bluuebunny/crossref_metadata_2025_split huggingface dataset:
Civilian Nuclear Accidents
Authors: Runde Wolfgang , Neu Mary P. , Goff George S. 
Published: December 2011

AbstractSince the discovery of plutonium and its use for nuclear weapons and nuclear energy radionuclides have been dispersed into the environment and contribute significantly to the global presence of anthropogenic radionuclides. Today, nuclear power plants are controlled by the national radiation protection authorities but are continuously emitting the small amounts of radioactivity permitted by the national health authorities. Other releases originate from the use of radionuclides in medical diagnostic and therapeutic treatments. Although these releases are minor compared to natural radioactivity and anthropogenic radionuclides, they contribute to the current radiation background. The anthropogenic actinides in the northern hemisphere mainly originated during nuclear weapons testing, fallout from the reactor accident at Chernobyl, atmospheric burnup of nuclear satellites, and intentional discharges of liquid waste streams from industrial‐scale nuclear reprocessing facilities. Despite the increasingly sophisticated engineered reactor and processing systems, accidents since the 1950s have resulted in the release of radioactivity to the environment. The most prominent accidents that led to a significant dispersion of radionuclides are the Three Miles Island accident, the Windscale Fire, and the Chernobyl accident. In this article, we discuss these events and other nonweapons related uncontrolled releases of radioactivity into the environment.
Photosynthesis: Energy Conversion
Authors: Ulas Gözde , Brudvig Gary W. 
Published: December 2011

AbstractThe process of water oxidation and carbon dioxide reduction in oxygenic photosynthesis involves a complex series of events that start with light energy capture and end with its storage in the form of the chemical energy in glucose. These reactions provide a solution to efficient solar energy conversion into high‐energy chemicals. The principles revealed by study of natural photosynthetic systems may be used to design artificial systems for solar fuel production. Understanding the light‐driven oxidation of water, in particular, is of high interest, as this half reaction could be used in sustainable solar fuel production by processes of artificial photosynthesis to meet the world's growing energy demand. In this article, we look into the intricate photosynthetic machinery and the various processes that it performs in order to efficiently capture, convert, and store light energy. Our main focus is on the so‐called “light” reactions, where specific processes are driven by direct light absorption. As a result, reducing equivalents are extracted from water and transferred to NADP+, to be used in the carbon‐fixing reactions, which are not directly modulated by sunlight. We describe the characteristic features of each protein in the photosynthetic electron‐transport machinery, and specifically focus on the water‐oxidation catalysis performed as the first step of oxygenic photosynthesis by the metalloenzyme photosystem II, due to its relevance to synthetic biomimetic water‐oxidation catalysts. Several processes that photosystem II employs to couple light energy absorption to catalytic turnover are discussed, including proton and electron transfers, redox leveling, charge accumulation, and proposed catalytic mechanisms.
Energy Research: Computational Challenges
Authors: Batista Victor S. 
Published: December 2011

AbstractThe emergence of photocatalytic solar cells based on semiconductor materials functionalized with earth‐abundant transition metal complexes represent a promising development for the sustainable production of fuel from renewable resources (e.g., water). This article reviews recent advances in studies of nanoporous TiO2 thin films sensitized with manganese catalysts, with emphasis on recent computational work integrated with synthesis, electrochemistry, and spectroscopy. The resulting interdisciplinary approach addresses fundamental aspects that affect the overall efficiency of photocatalytic mechanisms, including proton‐coupled electron transfer, rectification of interfacial electron transfer, and visible light absorption, providing guidelines for the design of novel photocatalytic materials for fuel production.
6‐Pyruvoyl‐Tetrahydropterin Synthase
Authors: Nar Herbert 
Published: December 2011

AbstractThe 6‐pyruvoyl‐tetrahydropterin synthase (PTPS), a zinc‐dependent, heat‐stable, homohexameric protein complex of approximately 90 kDa molecular weight catalyzes the conversion of dihydroneopterin triphosphate to 6‐pyruvoyl‐tetrahydropterin, the second of three enzymatic steps in the synthesis of tetrahydrobiopterin from GTP.The 6‐pyruvoyl‐tetrahydropterin synthetase monomer forms a compact, single‐domain α + β structure containing a sequential, four‐stranded, antiparallel β‐sheet. Oligomerization occurs through association of monomers via their β‐sheets that form a 12‐stranded β‐barrel structure that is duplicated in the functional hexameric form via a head‐to‐head association of two trimers.The PTPS active site is a 12‐Å deep cavity that is located on the interface of three monomers, two from one trimer and one subunit from the other trimer. The Zn(II) binding site is located at the center of the cavity. The transition metal is bound to the NE2 atoms of the three histidine residues. The role of the catalytic metal is to correctly position the substrate, to polarize the carbon–oxygen bonds for facile proton release from the substrate, and to prevent cleavage of the C1′‐C2′ substrate side‐chain bond.In addition, PTPS contains an intersubunit catalytic triad motif composed of the amino acid residues CysA42, HisB89, and AspB88 from two neighboring monomers (A and B) that putatively function as a relay system for proton abstraction from substrate and reaction intermediate. Residue GluA133 may represent the key residue for the stereospecificity of the catalyzed reaction.
E. coli Alkaline Phosphatase
Authors: Kantrowitz Evan R 
Published: December 2011

AbstractEscherichia colialkaline phosphatase (AP) is a metalloenzyme that catalyzes the nonspecific hydrolysis of phosphomonoesters. Because of the extensive functional and structural studies available on the AP fromE. coli, this enzyme has become the model for all APs. The two active sites of dimeric AP each contain binding sites for two Zn2+and one Mg2+. These metals are critical for dimer formation and catalytic activity. The reaction proceeds via a phosphoseryl intermediate formed by the attack of the hydroxyl oxygen of Ser102 on the phosphorus of the substrate. The substrate is stabilized in the active site by binding to Zn2+. In the second step of the double in‐line displacement mechanism, a hydroxyl bound to Zn2+hydrolyzes the phosphoseryl intermediate. Under basic conditions, the slow step in the mechanism is the release of phosphate from the noncovalent enzyme–phosphate complex. X‐ray structures of the free enzyme, the phosphoseryl intermediate, an enzyme–vanadate complex that mimics the transition state, and the enzyme–phosphate noncovalent complex have been used to delineate molecular details of the catalytic mechanism. Sequence alignments of APs from various species have been used to provide explanations for the enhanced activity of the mammalian APs as compared to the bacterial APs and why certain APs utilize Co2+in place of Zn2+. The molecular details of phosphate hydrolysis ascertained from the study of AP has applications to other enzymes that are involved in phosphate ester hydrolysis.
Structural Zinc Sites
Authors: Auld David S 
Published: December 2011

AbstractStructural 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

AbstractThe 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

Abstract

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

AbstractThe 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

AbstractLeishmanolysin 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

AbstractInverzincins 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

AbstractCaM 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

AbstractBM‐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

AbstractAnnexins 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

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

Abstractb‐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

AbstractFunctional ClassOccurrenceBiological FunctionAmino Acid Sequence InformationProtein Production, Purification, and CharacterizationMetal Content and CofactorsActivity TestSpectroscopyX‐Ray Structure ofPDRFunctional AspectsAcknowledgementsRelated Articles
Hemerythrin
Authors: Stenkamp Ronald E 
Published: December 2011

AbstractHemerythrin 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.