bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Zinc Sites
Authors: Auld David S
Published: December 2011

Structural zinc binding sites in proteins have a combination of four nitrogen, oxygen, and sulfur ligands provided by the side chains of amino acids of the protein. In marked contrast to catalytic zinc sites, no metal‐coordinated water molecule is present. There are over seven dozen representatives of structural zinc sites. While the sulfur of a cysteine is by far the preferred ligand for such sites, it is also found in combination with an imidazole nitrogen of a histidine, and/or a carboxylate oxygen from aspartate or glutamate. Of the 22 possible permutations of these 4 ligands, 8 have been observed. The ligands to these metal sites are provided by protein sequences as small as 10 amino acids and as large as 210 amino acids but the majority fall within the range of 25 to 50 amino acids. The ligands are frequently supplied from within or just before or after a β‐sheet secondary structure. The role of a structural zinc site is probably twofold. It maintains the structure of the protein in the immediate vicinity of the metal site. In this manner, it may influence enzymatic activity by providing active site residues involved in catalysis and/or affecting the chemical environment of catalytic groups through interaction with amino acids originating from within its metal‐binding spacers. However, in many cases these metal sites also affect the overall stability of the protein as judged by temperature and pH criteria.
Cys2His2Zinc Finger Proteins
Authors: Laity John H
Published: December 2011

The Cys2His2(C2H2) zinc finger is one of the simplest independently folded structural domains known, yet the number of proteins with distinct and complex functions that contain the motif is too large to count. The domain consists of a small antiparallel β‐sheet and a single helix that contribute two cysteine and two histidine ligands respectively to coordinate a central Zn(II) ion in a nearly perfect tetrahedral geometry. The C2H2 zinc finger is one of the major DNA binding motifs in eukaryotic transcription factors, and probably the most common protein motif in the human genome. DNA sequence specificity is achieved through residue side‐chain contacts to DNA bases that occur at preferential residue positions located in the N‐terminal region of the zinc finger helix (‘fingertip’) that reside primarily on one surface of the domain. Functional specificity and diversity of C2H2 zinc finger proteins are, paradoxically, both achieved through tandem repeats of the motif separated by short, conserved peptide linkers, where each individual finger is capable of recognizing a distinct DNA subsite. Diversity of the C2H2 motif extends beyond DNA recognition to protein–RNA and protein–protein interactions, although these functions are not well understood. Since the first reported structure of a single finger almost 15 years ago, over 40 C2H2 zinc finger structures have been reported both free and bound to DNA. Detailed molecular aspects of C2H2 zinc finger structure, function, and metal binding are examined.
Insulin
Authors: David Smith G
Published: December 2011

The protein hormone insulin, produced in the pancreas and stored in granules, interacts, after secretion into the blood stream, with the extracellular domain of the insulin receptor. This interaction initializes a signal transduction cascade that ultimately results in glucose absorption and metabolism. In the presence of zinc ion, insulin crystallizes as a threefold symmetric T
6
hexamer complexed to two zinc ions. When phenol,
m
‐cresol, or resorcinol is present in the crystallizing media, the first eight residues of all B‐chains undergo a conformational change from extended to α‐helical producing an R
6
hexamer. In the presence of thiocyanate or chloride ion, only residues 4 through 8 in the B‐chains of one trimer undergo the conformational change to produce a T
3
R
3
f
hexamer. This allosteric behavior of the insulin hexamer has been observed in the solid state as well as in solution. Like the T
6
hexamer, each zinc ion that lies on the crystallographic threefold axis is octahedrally coordinated by NE2s of three symmetry related HisB10 residues and three water molecules. Because of the conformational transition from T to either R or R
f
, there is not sufficient space in an R‐ or R
f
‐state trimer to accommodate octahedral coordination, and, therefore, zinc adopts tetrahedral coordination through bonds to the three symmetry related HisB10 NE2 atoms and either to a water molecule or to a chloride ion. In the case of T
3
R
3
f
hexamers, three additional zinc binding sites exist between symmetry related R
f
‐state monomers in which each zinc ion is coordinated by NE2 of a second orientation of the side chain of HisB10, NE2 of HisB5 of an adjacent monomer, and two chloride ions. From a total of 34 crystal structures of hexameric insulin, mean ZnNE2 bond distances of 2.00 or 2.10 Å are observed in tetrahedral or octahedral geometry, respectively.
Methionine Aminopeptidase
Authors: Matthews Brian W
Published: December 2011

The methionine aminopeptidases represent a novel class of metalloprotease generally having two cobalt ions in the active site. The proteins consist of two topologically similar domains folded with a ‘pita‐bread’ motif. Structural analysis of various inhibitor complexes with theEscherichia colienzyme and other members of the family have suggested a putative mechanism of catalysis related to that originally proposed for thermolysin.
Leishmanolysin
Authors: Metcalf Peter , Etges Robert
Published: December 2011

Leishmanolysin is a major surface antigen of the promastigote insect form of the parasitic protozoanLeishmania, and is thought to play a role preventing complement‐mediated lysis after infection of the mammalian host by the sand fly vector. Leishmanolysin is a ∼52 kDa membrane‐bound neutral zinc proteinase of the metzincin class, with some resemblance to collagenase in the active site region. Leishmanolysin can be inhibited by collagenase inhibitors but it does not cleave native collagen. Thein vivosubstrates have not been determined. The crystal structure, determined using protein purified fromLeishmania majorpromastigotes, revealed three domains where the N‐terminal domain has a similar fold to the catalytic domains of zinc proteinases and the central and cysteine‐rich C‐terminal domains have novel folds. The active site is located in a cleft between the N‐terminal and central domains. The molecule is attached to the outer membrane of the promastigote via a C‐terminal‐linked GPI anchor.
Pitrilysins/Inverzincins
Authors: Maskos Klaus
Published: December 2011

Inverzincins are characterized by an inverted zinc‐binding motif (HxxEH) rather than the classical zincin motif (HExxH). Pitrilysin fromEscherichia coliis the prototype of one subfamily, which also contains eukaryotic family members such as the insulin‐degrading enzyme (IDE) and theN‐arginine dibasic convertase (NRDc), both playing important roles in hormone metabolism and cellular regulation. The topology of active site residues shows some similarity to zincins, suggesting a convergent evolution for these types of metalloproteases. The closely related members of the mitochondrial processing peptidase (MPP) subfamily function as soluble heterodimers or as building blocks of the cytochrome c reductase complex and share the tendency with pitrilysin‐like enzymes to cleave peptides at hydrophobic or positively charged sites in a context‐dependent manner. For several family members, binding and cleavage of substrate is supposed to depend on secondary or tertiary structure and seems to proceed within a compartment formed by the respective enzyme.
Calmodulin
Authors: Yap Kyoko L , Ikura Mitsuhiko
Published: December 2011

CaM is a ubiquitous eukaryotic calcium binding protein that interacts with hundreds of proteins including kinases and phosphatases, transmembrane ion channels and pumps, and cytoskeletal regulatory proteins. In response to an increase in intracellular calcium, CaM undergoes a major conformational change enabling target binding and activation. In some cases, CaM is able to bind target proteins in the absence of, or independently of, Ca2+; in others, CaM binding may induce inactivation. The structural plasticity of calmodulin is demonstrated by the diversity observed in its interaction with various targets.
Basement Membrane ProteinBM‐40
Authors: Hohenester Erhard , Timpl Rupert
Published: December 2011

BM‐40, also known as SPARC or osteonectin, is a secreted glycoprotein present in all metazoa. The protein is expressed in tissues undergoing morphogenesis, remodeling, and repair.In vitro, BM‐40 binds to several collagens and is both antiproliferative and counteradhesive. Human BM‐40 consists of an acidic N‐terminal domain, a follistatin‐like (FS) domain, and an α‐helical (EC) domain that contains two functional EF‐hand calcium‐binding motifs. The crystal structure of the FS–EC domain pair has been determined. Calcium and collagen binding to the EC domain has been studied using site‐directed mutagenesis, spectroscopy, and binding assays.
Annexins: Calcium Binding Proteins with Unusual Binding Sites
Authors: Rosengarth Anja , Luecke Hartmut
Published: December 2011

Annexins comprise a multigene family of calcium‐ and phospholipid‐binding proteins. They are structurally divided into a conserved core domain and a flexible N‐terminal domain. The core domain contains four (in the case of annexin A6, eight) repeats, which fold into five α‐helices (named A through E) each. The overall shape of the annexin core is a curved disk with the calcium binding sites located on the concave face and the N‐terminal domain on the convex face. Annexins contain three different calcium binding sites: type II, type III, and AB′ sites. Type II and AB′ sites are found in the loops between the A and the B helix of each repeat. The coordination sphere for the calcium ion in the type II site generally comprises three backbone carbonyl oxygens, the side chain of an acidic residue 39 residues downstream of the AB loop, and two water molecules. The AB′ site is formed by one backbone carbonyl oxygen, one nearby acidic residue, and four to five water molecules. The calcium ion in the type III binding site, which is usually located in the loop between the D and E helix, is coordinated by two backbone carbonyl oxygens, one acidic residue nearby, and three to four water molecules. In comparison to EF hand calcium‐binding proteins, the affinity for calcium ions of annexins is rather low, which might be due to the large number of water molecules involved in the coordination of the calcium ions. In this review, we will give an overview on the structure and function of several mammalian annexins. We will also discuss in detail the coordination of calcium ions in the different types of calcium binding sites found in annexins.
Metal‐Dependent TypeIIRestriction Endonucleases
Authors: Vanamee Éva Scheuring , Aggarwal Aneel K
Published: December 2011

Type II restriction endonucleases are phosphodiesterases that bind double‐stranded DNA with high specificity and cleave both strands of the DNA to yield 5′‐phosphate and 3′‐hydroxyl groups as products utilizing Mg2+as a cofactor. Owing to their high specificity and extraordinary number (>3500 discovered), type II restriction enzymes have become indispensable tools in molecular biology and have been widely exploited for studying site‐specific protein–DNA interactions. Surprisingly, they share little or no sequence homology among them, though the three‐dimensional structures of the 14 restriction enzymes determined to date reveal a common‐core motif with a central β‐sheet that is flanked by α‐helices on both sides. The active sites occur at one end of the central β‐sheet and contain at least three superimposable residues that are critical for catalysis. The cleavage reaction occurs through an SN2 mechanism with an in‐line displacement of the 3′‐hydroxyl group and an inversion of configuration of the 5′‐phosphate group. However, there is uncertainty about the precise mechanism of cleavage, especially regarding the number of metals involved in catalysis.
Cytochromec7
Authors: Banci Lucia , Assfalg Michael
Published: December 2011

Functional Class

Occurrence

Biological Function

Amino Acid Sequence Information

Protein Production, Purification and Molecular Characterization

Metal Content and Cofactors

Spectroscopy

Structural Studies

Functional Aspects

Related Articles
b‐Type Cytochrome Electron Carriers: Cytochromesb562andb5, and Flavocytochromeb2
Authors: Mathews F Scott
Published: December 2011

b‐Type cytochromes form a class of proteins that contain a heme (iron‐protoporphorin IX) bound non‐covalently to its polypeptide chain with two of its side chains coordinated to the iron. One of these side chains is always histidine and the other can be histidine or methionine. Cytochromes b5and b562are simple mono‐domain proteins that contain heme as the only prosthetic group and histidine and methionine, respectively, as the second heme ligand. Flavocytochrome b2also contains histidine as the second heme ligand, but contains a second prosthetic group, flavin mononucleotide (FMN), that resides in a separate domain. Cytochromes b5and b562each mediate intracellular electron transfer between redox partners, the former within the endoplasmic reticulum of mammalian cells and the latter within bacteria. Flavocytochrome b2catalyzes the oxidation of lactic acid within yeast mitochondria, with the cytochrome domain mediating electron transfer from substrate‐reduced FMN to exogenous cytochrome c. The structural, electrochemical, and catalytic properties of these three proteins are presented, along with the results of mutagenesis.
Phthalate Dioxygenase Reductase
Authors: Ludwig Martha L , Ballou David P , Noodleman Louis
Published: December 2011

Functional Class

Occurrence

Biological Function

Amino Acid Sequence Information

Protein Production, Purification, and Characterization

Metal Content and Cofactors

Activity Test

Spectroscopy

X‐Ray Structure ofPDR

Functional Aspects

Acknowledgements

Related Articles
Hemerythrin
Authors: Stenkamp Ronald E
Published: December 2011

Hemerythrin is a non‐heme iron protein that serves as an oxygen transfer or storage protein in several marine invertebrate phyla (sipunculids, brachiopods, priapulids and annelids). Each protein subunit (13 500 kD) binds two iron atoms by histidine, aspartic acid, and glutamic acid side‐chains. The protein carboxylates and a μ‐oxygen atom bridge the iron atoms in a prototypic FeOFe complex that has been extensively studied. One iron binds exogenous ligands including dioxygen and small anions. The protein functions by reversibly adding dioxygen to a deoxy form containing ferrous iron to produce an oxy form containing ferric iron and a peroxo anion.
Methane Monooxygenase Hydroxylase
Authors: Whittington Douglas A , Lippard Stephen J
Published: December 2011

Soluble methane monooxygenase (sMMO) catalyzes the conversion of methane and dioxygen to methanol and water. It is a cytoplasmic system of three proteins produced in methanotrophic bacteria grown under conditions of low copper stress. The best characterized sMMO stems fromMethylococcus capsulatus(Bath). Under physiological conditions inM. capsulatus(Bath), three protein components are required for sMMO activity. These included a 251‐kDa hydroxylase (MMOH), which contains the carboxylate‐bridged, dinuclear iron active site; a 16‐kDa regulatory protein known as protein B (MMOB); and a 38.6‐kDa reductase (MMOR) that contains FAD and a Fe2S2center. MMOH has been characterized by several spectroscopic techniques (UV/vis, X‐ray absorption, Mössbauer, EPR, ENDOR, CD, MCD), which established the nature of the dinuclear iron active site.

The crystal structure of the MMOH component of sMMO fromM. capsulatus(Bath) has been solved in two crystal forms, one of which was refined to a resolution of 1.7 Å. The enzyme is composed of two copies each of three subunits (α2ß2γ2), and all three subunits are almost completely α‐helical. The active site of each α‐subunit contains one dinuclear iron center, housed in a four‐helix bundle. The two iron atoms are octahedrally coordinated by 2 histidine and 4 glutamic acid residues, as well as by a bridging hydroxide ion, a terminal water molecule, and at 4°C, a bridging acetate ion, which is replaced at −160°C with a bridging water molecule. Comparison of the results of the two crystal forms shows one structural difference, namely, the altered side chain conformation of Leu110 at the active site cavity. It is suggested that this residue serves as one component of a hydrophobic gate controlling the access of substrates to and products from the active site. MMOB and MMOR bind to the α‐ and ß‐subunits of MMOH, respectively. The structure of MMOB has been known from NMR. X‐ray structures of reduced MMOH and of DMSO‐soaked MMOH have been determined. During the turnover, Hperoxoand Q intermediate states could be trapped and structures proposed from density functional theory studies.
Peptide Deformylase
Authors: Becker Andreas , Kabsch Wolfgang
Published: December 2011

Peptide deformylase (EC 3.5.1.31) is a mononuclear iron enzyme that cleaves the formyl group of theN‐terminal formyl‐methionine residue of nascent polypeptide chains in eubacteria. It is strictly stereospecific for aL‐amino acid as the first residue of formyl‐peptide substrates and strongly prefers substrates with at least two or more residues. The native enzyme fromEscherichia coliis a monomeric protein of 168 amino acid residues that contains one tightly bound Fe2+ion. The metal ion is tetrahedrally coordinated by a water molecule and the side chains of residues Cys90, His132, and His136. Similar to thermolysin, the two histidines are part of the HEXXH motif and the glutamate residue is required for enzymatic activity. The native iron form of peptide deformylase is extremely sensitive to oxidative destruction. On substitution of the iron ion by Ni2+or Co2+the enzyme is insensitive to oxidation and maintains its activity, whereas the Zn2+form is nearly inactive.
ConcanavalinA
Authors: Kalb (Gilboa) A Joseph , Helliwell John R
Published: December 2011

Concanavalin A is a metalloprotein containing manganese and calcium in a bimetallic metal‐binding site. As isolated from the Jack bean (Canavalia ensiformis), the protein binds saccharides such as α‐methyl mannoside and α‐methyl glucoside. Acid treatment produces a demetallized form that does not bind saccharides and that which can be remetallized to produce various metal‐substituted forms, such as (Ni, Ca), (Co, Ca), (Cd, Ca), (Zn, Ca), and (Cd, Cd). Structural studies of the crystal structures of the native, demetallized, and remetallized proteins, as well as its complexes with saccharides, have helped clarify the nature of the interaction between the metal‐binding site and the saccharide‐binding site. The protein has been well‐characterized structurally, namely, at an X‐ray crystallographic resolution of 0.94 Å (Mn, Ca form), by neutron protein crystallography to define the hydration details (at 2.4 Å resolution), by molecular dynamics to better define the protein saccharide recognition, by EPR using the manganese d5 high spin state, and by EXAFS (Zn, Ca form). These structural characterizations include studies at 12 K, 100 K, and room temperature.
MethylmalonylCoAMutase
Authors: Gruber Karl , Kratky Christoph
Published: December 2011

The 5′‐adenosylcobalamin dependent methylmalonyl‐CoA mutase (MCM) catalyzes the reversible and stereospecific equilibration of (2R)‐methylmalonyl CoA and succinyl CoA through a radical mechanism. Its occurrence ranges from bacteria to mammals, where it is required for the metabolism or biosynthesis of propionate. MCM fromPropionibacterium shermaniiis an αβ‐heterodimer of total molecular weight 150 kDa, containing an inactive β‐subunit along with an active α‐subunit, the latter binding one adenosylcobalamin molecule close to the active site. The protein was found to occur in two fundamentally different conformations: in the presence of substrates it crystallizes in a “closed” conformation, whereas in the absence of substrates an “open” conformation is observed. This dramatic conformational change suggests a mechanism for the first step of the MCM‐catalyzed reaction cycle, i.e. the substrate‐induced homolysis of the Co–C bond.
Cucumber Basic Protein
Authors: Guss J Mitchell , Freeman Hans C
Published: December 2011

The ‘blue’ or ‘type 1’ copper protein family has several sub‐families. One of these sub‐families, the phytocyanins, has several sub‐sub‐families: plantacyanins, stellacyanins, and uclacyanins. The cucumber basic protein, now known as cucumber plantacyanin, was the first structurally characterized as phytocyanin. As in the archetypal ‘blue’ copper protein plastocyanin, the copper atom in cucumber plantacyanin is coordinated by the side chains of two histidines, one cysteine, and one methionine. The polypeptide has a β‐sandwich fold resembling that of plastocyanin, with the exception that one hairpin is bent at a right angle to the rest of the β‐sandwich. As a result, the copper site is more exposed to solvent than in other ‘blue’ copper proteins. The biological functions of phytocyanins are still uncertain.
Tetraheme CytochromesC3
Authors: Bento Isabel , Louro Ricardo O , Soares Cláudio M , Carrondo M Arménia
Published: December 2011

Tetraheme cytochromesc3constitute the best‐studied group among the multiheme cytochromes belonging to the class III of Ambler's classification. Since 1954, when cytochromec3was isolated fromDesulfovibrio vulgarisfor the first time by Postgate, these proteins have been widely characterized, especially those from theDesulfovibrio(D.) genus. All these cytochromes have their heme group attached to the polypeptide chain by cysteine residues and show bis‐histidinyl coordination of the heme iron and a highly conserved heme‐binding motif (CXXCH or CXXXXCH). Cytochromesc3show a wide variety of redox potentials, ranging from 0 to −400 mV, are usually periplasmatic proteins, and are believed to play key roles in the electron transfer chains. Recently, the cytochromec3group was divided into two main types on the basis of structural, functional, and genetic differences: type I cytochromec3(TpI‐c3) and type II cytochromec3(TpII‐c3). This paper reviews their structural, spectroscopic, and functional properties, based on the wealth of information currently available. These include physicochemical properties, redox mechanisms, coupling between electron and proton transfer, and data concerning the interaction with their redox partners obtained by experimental and molecular modeling methods.
TheNrfHCytochromecQuinol Dehydrogenase
Authors: Rodrigues Maria Luisa , Pereira Inês AC , Archer Margarida
Published: December 2011

NrfH is a membrane‐anchored tetraheme cytochromecthat oxidizes menaquinol and transfers electrons to the cytochromecnitrite reductase, NrfA. It belongs to a family of cytochromecquinol dehydogenases, known as theNapC/NirT family, which plays an important role in bacterial anaerobic respiration. Here, we describe the major structural and biochemical features of NrfH that has been isolated in the form of a native NrfHA complex from someProteobacteriaspecies. The notable heme coordination of NrfH, revealed uponDesulfovibrio vulgarisNrfHA structure determination, is discussed in light of primary structure analysis within the NrfH proteins and within the family of cytochromecquinol dehydogenases. Interestingly, NrfH shows a higher sequence variation than other members of the NapC/NirT family. The crystal structure of NrfHA bound to the HQNO inhibitor is also presented and analyzed together with inhibition studies.
BAK
Authors: Moldoveanu Tudor , Liu Qian , Green Douglas R , Gehring Kalle
Published: December 2011

The effector BCL‐2 (B cell lymphoma‐2) protein BAK (B cell lymphoma‐2 homologous antagonist/killer) directly mediates mitochondrial outer membrane permeabilization to drive the mitochondrial pathway of apoptosis. The structures of BAK are presented to reveal two different modes of homodimerization. Noncovalent dimerization is mediated by one Zn2+atom to inhibit the release of cytochromecfrom mitochondrial intermembrane space. Covalent oxidative homodimerization occurs through disulfide bond formation at Cys166 and is thought to prevent the Zn2+‐mediated inhibition by abolishing the Zn2+‐dependent homodimerization interface. Neither mode of dimerization affects the putative B cell lymphoma‐2 homology 3 (BH3)‐binding pocket, which remains occluded in BAK to preclude high affinity BH3 peptide binding.
The Sodium PotassiumATPase
Authors: Nyblom Maria , Morth Jens Preben , Nissen Poul
Published: December 2011

At the expense of adenosine triphosphate (ATP), the P‐type ATPase family of membrane proteins actively transports different cations or lipids, in a reaction cycle that includes the phosphorylation/dephosphorylation of a conserved aspartate residue. These proteins share a common structural and mechanistic core, but Na+, K+‐ATPase is the first multisubunit P‐type ATPase to be structurally determined. The Na+, K+‐ATPase exports three Na+‐ ions per ATP molecule from the cytoplasm, while at the same time transporting two K+‐ ions in the opposite direction. This electrogenic pump is critical for human and animal cells where the gradients of these ions are important for maintaining the resting potential and for electrical excitability of e.g. muscle and nerve cells, and for energization of secondary transporters and osmotic control. This article reviews the currently available structural knowledge of the Na+, K+‐ATPase. Hitherto, there are only structures of one of the catalytic forms reported representing the potassium‐occluded state ([K2]E2·Pi). The overall architecture of the αβγ‐complex is presented and the differences compared to the previously characterized structures of the sarco(endo)plasmic reticulum Ca2+‐ATPase (SERCA) are pinpointed. Furthermore, the properties of the K+‐ion binding sites are described and the functional relevance of the C‐terminus is addressed.
Potassium Channels
Authors: Lenaeus Michael J , Gross Adrian
Published: December 2011

Potassium channels are membrane proteins that allow for and regulate the passive flow of potassium ions in and out of cells. Potassium channels are often multidomain proteins consisting of a central ion‐conducting pore domain and peripheral gating domains sensitive to channel‐specific stimuli (e.g., voltage). This article deals with the structure of the pore domain, where important ion–protein interactions occur. Several structures of potassium channel pore domains have been published and these are discussed herein, along with the current hypotheses regarding channel function, gating, and ion movement.
Corrinoid Adenosyltransferases
Authors: Mera Paola E. , Rayment Ivan , Escalante‐Semerena Jorge C.
Published: December 2011

ATP corrinoid adenosyltransferase (ACA) enzymes catalyze the transfer of the adenosyl moiety from ATP to cob(I)alamin, resulting in the formation of the unique organometallic C–Co bond characteristic of coenzyme B
12
(adenosylcobalamin, AdoCbl). In the last decade, our knowledge of how these enzymes catalyze the adenosylation of cobalamin has grown rapidly. ACA enzymes also facilitate the thermodynamically unfavorable reduction of cob(II)alamin. Studies with ACA enzymes revealed an unprecedented four‐coordinate square‐planar corrinoid conformation. ACA enzymes bring the reduction potential of cob(II)alamin to within physiological range by generating the four‐coordinate Co(II) corrinoid species. Recently, visual evidence of the existence of a Co(II) corrinoid species was obtained when the 3D crystal structure of the human‐type ACA enzyme was solved with ATP and cob(II)alamin bound in the active site. To date, three types of ACA enzymes have been identified, CobA, PduO, and EutT. The PduO‐type is the most widely distributed ACA enzyme and is the form found in humans where ACA enzymes play an essential role in metabolism; malfunctioning of this enzyme cause severe health defects. Detailed analyses of the catalytic mechanism of ACA enzymes have provided an understanding of how some mutations in the human ACA enzyme render it inactive.
DNA
‐Binding Proteins From Starved Cells (
Dps
Proteins)
Authors: Stefanini Simonetta , Ceci Pierpaolo , Ardini Matteo , Ilari Andrea
Published: December 2011

In the recent past over 200 Dps (DNA‐binding proteins from starved cells) proteins have been identified in bacterial genomes. Dps proteins belong to the ferritin superfamily. They are expressed under conditions of oxidative and/or nutritional stress and are characterized by a highly conserved shell‐like structure of 12 identical subunits assembled with 23 symmetry. The internal cavity is designed to accommodate up to 500 iron/atoms per molecule in a soluble and bioavailable form. Dps proteins play an important role in the complex protection mechanism against oxidative damage. The presence of a highly conserved ferroxidase center, which uses hydrogen peroxide as physiological iron oxidant, confers to all Dps proteins the capacity to decrease the production of the hydroxyl‐radicals and, hence, to prevent the damage to DNA and other cellular components. Ferroxidase activity is of special importance in pathogenic bacteria since production of hydrogen peroxide in macrophages and neutrophiles represents one of the first host defense mechanisms. The capacity to bind DNA in a nonspecific manner and pack it into condensed structures, an attribute limited to some members of the family, represents the second distinctive mechanism used to advantage by Dps proteins for the survival of the organism.
Calmodulin Interactions withCav1 andCav2 Voltage‐Gated Calcium ChannelIQDomains
Authors: Kim Eun Young , Findeisen Felix , Minor Daniel L
Published: December 2011

High‐voltage‐activated calcium channels (CaV1s and CaV2s) are transmembrane protein complexes that couple membrane depolarization to cellular calcium entry. Because calcium is an intracellular messenger and CaVs are important calcium sources, CaVs have a key role in the conversion of electrical signals into the chemical signaling cascades that drive a variety of vital physiological processes in nerve and muscle. These include excitation‐contraction coupling, hormone release, gene regulation, and synaptic transmission. CaVs are regulated by a diverse set of feedback mechanisms. Two important forms of activity‐dependent feedback modulation involve interactions between calcium‐calmodulin (Ca2+/CaM) and the CaVα1pore‐forming subunit of CaV1s and CaV2s: calcium‐dependent inactivation (CDI) in which calcium influx promotes channel closing following activation, and calcium‐dependent facilitation (CDF), a process that enhances channel opening in response to elevated cytoplasmic calcium. The main site of action for Ca2+/CaM is a motif, known as anIQ domain, located on the C‐terminal cytoplasmic tail of the CaVα1pore‐forming subunit. Strikingly, different Ca2+/CaM lobes are responsible for CDI and CDF in CaV1 and CaV2 channels. Crystallographic studies have indicated a structural basis for the apparent inversion of lobe‐specific roles in CDI and CDF in which Ca2+/CaM binds CaV1 and CaV2 IQ domains in opposite orientations.
Mo–Se‐Containing Nicotinate Dehydrogenase
Authors: Dobbek Holger , Pierik Antonio J
Published: December 2011

Se Mo‐containing nicotinate dehydrogenase (NDH) of the anaerobic soil bacteriumEubacterium barkericatalyzes the hydroxylation of nicotinate with water and NADP+to 6‐hydroxynicotinate, one proton, and NADPH. This reaction is the first step in the degradation of nicotinate to pyruvate and propionate in a unique fermentation pathway. NDH is constituted by four different subunits and contains a Mo‐bound pyranopterin cofactor linked to cytosine dinucleotide, two different [2Fe2S] centers, and flavin adenine dinucleotide to facilitate the transfer of a hydride ion on NADP+. NDH is a member of the family of molybdenum hydroxylases and shares several distinctive features with other members of this enzyme family, such as xanthine oxidoreductase, aldehyde oxidase, and the Mo‐containing carbon monoxide dehydrogenase. The reactivity of NDH critically depends on the presence of selenium in the active site, where it is bound as a labile nonselenocysteinyl selenium ligand to molybdenum. The role of the selenium ligand is likely to accelerate the formal hydride transfer from the substrate into the Mo Se bond, displaying a novel reactivity of selenium in nature.
Symmetry and Steric Effects on Spin States in Transition Metal Complexes
Authors: Meier Ryan M. , Hanusa Timothy P.
Published: December 2011

Changes in the magnetic characteristics of transition metal complexes, particularly, their metal spin states, are most commonly achieved by varying the electron donor/acceptor properties of coordinated ligands. In some systems, it is possible to increase the steric bulk of ligands so that intramolecular crowding leads to changes in metal‐ligand bond distances; longer bonds produce weaker ligand fields and stabilize high‐spin or spin‐crossover complexes. Steric effects are also often associated, albeit indirectly, with a mechanism for influencing spin states that relies on modifying the symmetry‐based interactions of metal and ligand orbitals. Particular ligand orientations, as in bis(indenyl) compounds [M(R
9
C
7
)
2
], can be changed as the result of interligand steric pressure or crystal packing effects; such differences can alter metal d‐orbital energy levels and hence the stability of spin states. Both steric and symmetry effects add to the repertoire of techniques that can be used to control magnetic properties in transition metal complexes.
Biocompatible Nanoparticles with Aggregation‐Induced Emission Characteristics as Far‐Red/Near‐Infrared Fluorescent Bioprobes for In Vitro and In Vivo Imaging Applications
Authors: Qin Wei , Ding Dan , Liu Jianzhao , Yuan Wang Zhang , Hu Yong , Liu Bin , Tang Ben Zhong
Published: December 2011

Light emission of 2‐(2,6‐bis((E)‐4‐(diphenylamino)styryl)‐4H‐pyran‐4‐ylidene)malononitrile (TPA‐DCM) is weakened by aggregate formation. Attaching tetraphenylethene (TPE) units as terminals to TPA‐DCM dramatically changes its emission behavior: the resulting fluorogen, 2‐(2,6‐bis((E)‐4‐(phenyl(4′‐(1,2,2‐triphenylvinyl)‐[1,1′‐biphenyl]‐4‐yl)amino)styryl)‐4H‐pyran‐4‐ylidene)malononitrile (TPE‐TPA‐DCM), is more emissive in the aggregate state, showing the novel phenomenon of aggregation‐induced emission (AIE). Formulation of TPE‐TPA‐DCM using bovine serum albumin (BSA) as the polymer matrix yields uniformly sized protein nanoparticles (NPs) with high brightness and low cytotoxicity. Applications of the fluorogen‐loaded BSA NPs for in vitro and in vivo far‐red/near‐infrared (FR/NIR) bioimaging are successfully demonstrated using MCF‐7 breast‐cancer cells and a murine hepatoma‐22 (H22)‐tumor‐bearing mouse model, respectively. The AIE‐active fluorogen‐loaded BSA NPs show an excellent cancer cell uptake and a prominent tumor‐targeting ability in vivo due to the enhanced permeability and retention effect.
Risk of intraparenchymal hemorrhage with magnetic resonance imaging‐defined leukoaraiosis and brain infarcts
Authors: Folsom Aaron R. , Yatsuya Hiroshi , Mosley Thomas H. , Psaty Bruce M. , Longstreth W. T.
Published: December 2011

Objective:

To determine whether the burden of leukoaraiosis and the number of brain infarcts, defined by magnetic resonance imaging (MRI), are prospectively and independently associated with intraparenchymal hemorrhage (IPH) incidence in a pooled population‐based study.

Methods:

Among 4,872 participants initially free of clinical stroke in the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study, we assessed white matter grade (range, 0–9), reflecting increasing leukoaraiosis, and brain infarcts using MRI. Over a median of 13 years of follow‐up, 71 incident, spontaneous IPH events occurred.

Results:

After adjustment for other IPH risk factors, the hazard ratios (95% confidence intervals) across white matter grades 0 to 1, 2, 3, and 4 to 9 were 1.00, 1.68 (0.86–3.30), 3.52 (1.80–6.89), and 3.96 (1.90–8.27), respectively (p for trend <0.0001). These hazard ratios were weakened only modestly (p for trend = 0.0003) with adjustment for MRI‐defined brain infarcts. The IPH hazard ratios for 0, 1, 2, or ≥3 MRI‐defined brain infarcts were 1.00, 1.97 (1.10–3.54), 2.00 (0.83–4.78), and 3.12 (1.31–7.43) (p for trend = 0.002), but these were substantially attenuated when adjusted for white matter grade (p for trend = 0.049).

Interpretation:

Greater MRI‐defined burden of leukoaraiosis is a risk factor for spontaneous IPH. Spontaneous IPH should be added to the growing list of potential poor outcomes in people with leukoaraiosis. ANN NEUROL 2012;
Demyelination affects temporal aspects of perception: An optic neuritis study
Authors: Raz Noa , Dotan Shlomo , Chokron Sylvie , Ben‐Hur Tamir , Levin Netta
Published: December 2011

Objective:

Visual Evoked Potentials (VEPs) following optic neuritis (ON) remain chronically prolonged, although standard visual tests indicate full recovery. We hypothesized that dynamic visual processes, such as motion perception, may be more vulnerable to slowed conduction in the optic nerve, and consequently be better associated with projection rates.

Methods:

Twenty‐one patients with acute unilateral, first‐ever ON were studied during 1 year. Static visual functions (visual acuity, color perception, visual field, and contrast sensitivity), dynamic visual functions (motion perception), and VEPs were assessed repeatedly.

Results:

Visual and electrophysiological measurements reached maximal performance 4 months following the acute phase, with no subsequent improvement. Whereas VEP amplitude and static visual functions recovered, VEP latency remained significantly prolonged, and motion perception remained impaired throughout the 12‐month period. A strong correlation was found between VEP latencies and motion perception. Visual performance at 1 month was strongly predictive of visual outcome. For static functions, patients who showed partial recovery at 1 month subsequently achieved full recovery. For dynamic functions, the rate of improvement was constant across patients, independent of the initial deficit level.

Interpretation:

Conduction velocity in the visual pathways correlated closely with dynamic visual functions, implicating the need for rapid transmission of visual input to perceive motion. Motion perception level may serve as a tool to assess the magnitude of myelination in the visual pathways. The constancy across patients may serve as a baseline to assess the efficacy of currently developing neuroprotective and regenerative therapeutic strategies, targeting myelination in the central nervous system. ANN NEUROL 2012
Implication of perturbed axoglial apparatus in early pediatric multiple sclerosis
Authors: Dhaunchak Ajit Singh , Becker Christopher , Schulman Howard , De Faria Omar , Rajasekharan Sathyanath , Banwell Brenda , Colman David R. , Bar‐Or Amit ,   on behalf of the Canadian Pediatric Demyelinating Disease Group
Published: December 2011

Cerebrospinal fluid samples collected from children during initial presentation of central nervous system inflammation, who may or may not subsequently be diagnosed as having multiple sclerosis (MS), were subjected to large‐scale proteomics screening. Unexpectedly, major compact myelin membrane proteins typically implicated in MS were not detected. However, multiple molecules that localize to the node of Ranvier and the surrounding axoglial apparatus membrane were implicated, indicating perturbed axon–glial interactions in those children destined for diagnosis of MS. Ann Neurol 2012;
Enhancing the affinity of SEB‐binding peptides by repeating their sequence
Authors: Dudak Fahriye Ceyda , Kılıç Nesrin , Demir Kadir , Yaşar Fatih , Boyacı İsmail Hakkı
Published: December 2011

The utilization of peptide ligands in biosensors and bioassays is dependent on achieving high affinity of these peptides toward their targets. In a previous report, we identified 12‐mer peptides that could selectively bind to Staphylococcal enterotoxin B (SEB) using a phage‐display library. In this study, we explore for new modification approaches to enhance the affinity of two different SEB‐binding peptides. In order to identify the binding regions of selected peptides, the charged residues and the ones, critical for the structure of peptide, were replaced with alanine. However, a specific binding region could not be suggested as all mutant peptides have lost their affinities toward SEB completely. The modifications for the affinity enhancement were done by repeating the 12‐mer peptide sequences. A 10‐fold increase was observed in the binding affinity of one of the two‐repeated peptides, while this modification did not affect the affinity of the other tested peptide. The peptide, with enhanced affinity, was further modified as three repeats; however the affinity of the peptide decreased. The structural basis of the affinity difference between modified peptides was examined by molecular dynamics simulation. The results showed that the conformational differences hold the key for affinity of peptides modified by repeating the sequence. This high affinity peptide with increased affinity is a promising molecular recognition agent to be used in the detection of SEB to be utilized in biosensing systems. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 98: 145–154, 2012.
Cross‐case Methodology: Bringing Rigour to Community and Systems Change Research and Evaluation
Authors: Lee Kien S. , Chavis David M.
Published: December 2011

Cross‐case study methodology is a more appropriate and still rigorous methodology for community and systems change research and evaluation. It supports learning about effective implementation, community capacity building, and resident engagement—all core elements of community and systems change efforts. It also communicates more effectively to non‐researchers and evaluators if, how, and why community and systems change occurred through the use of a narrative that combines qualitative and quantitative data to tell a story. The application of the cross‐case study methodology, adapted from Yin's cross‐case synthesis approach, requires five essential steps: developing a theory of change, establishing a measurement framework that reflects methodological and data source triangulation, developing a cross‐case study protocol and building a database, analysing and interpreting the findings, and communicating the results. This methodology was applied to the evaluation of the Safe Start Demonstration Project, a national community and systems change effort funded by the US Department of Justice, Office of Juvenile Justice and Delinquency Prevention. This methodology has all the attributes of scientific rigour. In this paper, we argue for a reconsideration of case study research by funders, policymakers, researchers, and evaluators and advance the cross‐case methodology as the emerging standard for community and systems change research and evaluation. Copyright © 2011 John Wiley & Sons, Ltd.
Responsive Vesicles from the Self‐Assembly of Crystalline‐Coil Polyferrocenylsilane‐block‐Poly(ethylene Oxide) Star‐Block Copolymers
Authors: Schacher Felix H. , Elbert Johannes , Patra Sanjib K. , Mohd Yusoff Siti F. , Winnik Mitchell A. , Manners Ian
Published: December 2011

We demonstrate the synthesis and characterization of star‐shaped crystalline‐coil block copolymers with four arms consisting of an inner block of poly(ethylene oxide) and an outer semicrystalline compartment of poly(ferrocenyldimethylsilane), [PEO50‐b‐PFDMS35]4. The materials were synthesized by transition‐metal‐catalyzed ring‐opening polymerization of dimethylsila[1]ferrocenophane in the presence of silane‐functionalized four‐arm PEO stars as macroinitiators and they exhibited a moderate polydispersity (PDI≅1.4). Self‐assembly in mixtures of THF and different alcohols as selective solvents for the PEO block resulted in the formation of semicrystalline vesicles (ethanol, 1‐butanol) or large, rather ill‐defined, spherical structures (methanol). Further, both the rate of addition of the selective co‐solvent and the overall solvent/non‐solvent ratio drastically affected the size and stability of the self‐assembled particles. We could also show that a photoacid generator, as a model for an active substance, can be encapsulated and the UV‐induced generation of HCl resulted in a straightforward degradation of the organometallic vesicles.
Staining of Fluid‐Catalytic‐Cracking Catalysts: Localising Brønsted Acidity within a Single Catalyst Particle
Authors: Buurmans Inge L. C. , Ruiz‐Martínez Javier , van Leeuwen Sanne L. , van der Beek David , Bergwerff Jaap A. , Knowles William V. , Vogt Eelco T. C. , Weckhuysen Bert M.
Published: December 2011

A time‐resolved in situ micro‐spectroscopic approach has been used to investigate the Brønsted acidic properties of fluid‐catalytic‐cracking (FCC) catalysts at the single particle level by applying the acid‐catalysed styrene oligomerisation probe reaction. The reactivity of individual FCC components (zeolite, clay, alumina and silica) was monitored by UV/Vis micro‐spectroscopy and showed that only clay and zeolites (Y and ZSM‐5) contain Brønsted acid sites that are strong enough to catalyse the conversion of 4‐fluorostyrene into carbocationic species. By applying the same approach to complete FCC catalyst particles, it has been found that the fingerprint of the zeolitic UV/Vis spectra is clearly recognisable. This almost exclusive zeolitic activity is confirmed by the fact that hardly any reactivity is observed for FCC particles that contain no zeolite. Confocal fluorescence microscopy images of FCC catalyst particles reveal inhomogeneously distributed micron‐sized zeolite domains with a highly fluorescent signal upon reaction. By examining laboratory deactivated FCC catalyst particles in a statistical approach, a clear trend of decreasing fluorescence intensity, and thus Brønsted acidity, of the zeolite domains is observed with increasing severity of the deactivation method. By comparing the average fluorescence intensities obtained with two styrenes that differ in reactivity, it has been found that the Brønsted acid site strength within FCC catalyst particles containing ZSM‐5 is more uniform than within those containing zeolite Y, as confirmed with temperature‐programmed desorption of ammonia.
ChemInform Abstract: Germanium Selenophosphates: The Incommensurately Modulated 1∞ [Ge4‐xPxSe124‐] and the Molecular [Ge2P2Se14]6‐.
Authors: Morris Collin D. , Malliakas Christos D. , Kanatzidis Mercouri G.
Published: December 2011

The one‐dimensional metastable compound (III) crystallizes in the monoclinic space group P21/c with Z = 1 (single crystal XRD).
ChemInform Abstract: Facile Synthesis of Zero‐, One‐, and Two‐Dimensional Vanadyl Pyrophosphates.
Authors: Solis‐Ibarra Diego , Silvia Jared S. , Jancik Vojtech , Cummins Christopher C.
Published: December 2011

The structures of (III) and (VI) are determined by single crystal XRD.
ChemInform Abstract: Chiral Sulfoxide‐Olefin Ligands: Completely Switchable Stereoselectivity in Rhodium‐Catalyzed Asymmetric Conjugate Additions.
Authors: Chen Guihua , Gui Jiangyang , Li Liangchun , Liao Jian
Published: December 2011

The new catalyst system is also applicable to aliphatic boronic acid (IIf).
ChemInform Abstract: Indium‐Catalyzed Construction of Polycyclic Aromatic Hydrocarbon Skeletons via Dehydration.
Authors: Kuninobu Yoichiro , Tatsuzaki Tomohiro , Matsuki Takashi , Takai Kazuhiko
Published: December 2011

A number of polycyclic aromatic hydrocarbons is available.
ChemInform Abstract: Gold‐Catalyzed Cyclization of Nonterminal Propargylic Amides to Substituted Alkylideneoxazolines and ‐oxazines.
Authors: Hashmi A. Stephen K. , Schuster Andreas M. , Schmuck Martin , Rominger Frank
Published: December 2011

Cyclization of nonterminal propargylic amides is achieved using a AuCl(IPr)—AgOTos catalytic system.
ChemInform Abstract: Development of PhSCF2CF2SiMe3 as a Tandem Anion and Radical Tetrafluoroethylene Equivalent: Preparation of Tetrafluoroethyl‐Substituted Alcohols and Tetrafluorotetrahydropyrans.
Authors: Chernykh Yana , Hlat‐Glembova Katarina , Klepetarova Blanka , Beier Petr
Published: December 2011

Title tetrafluoroethylene reagent contains an anionic and a radical CF2 side.