bluuebunny/crossref_metadata_2025_split huggingface dataset:
Water Splitting: Thermochemical
Authors: T‐Raissi Ali 
Published: December 2011

AbstractHydrogen can be produced by direct or single‐step splitting of water. The Gibbs free energy change for direct thermochemical water splitting is zero at about 4300 K at 1 bar. However, in practice, direct thermochemical splitting of water poses challenging high‐temperature materials and product separation issues, among others. One way to lower the extremely high temperatures required for direct splitting of water and mitigate gas separation issues is the use of multistep cycles. To date, more than 350 thermochemical cycles for splitting water has been conceived. Of these, fewer than two dozen cycles still remain subject to further research and development. Among them are several “sulfur family” cycles as well as a number of volatile and nonvolatile metal oxide cycles. All of these cycles consist of at least two process steps, and some are hybrid cycles requiring both heat and work (e.g., electricity) input. This article presents a brief review of the status of multistep thermochemical water‐splitting cycles (TCWSCs) for the production of hydrogen.
NucleaseP1
Authors: Volbeda Anne , Romier Christophe , Suck Dietrich 
Published: December 2011

AbstractNuclease P1 of the moldPenicillium citrinumis a zinc‐dependent enzyme that cleaves all PO3′ bonds in single‐stranded DNA and RNA substrates, independent of base sequence. Crystallographic studies of the native enzyme have shown that the trinuclear zinc active site is inaccessible for phosphate groups in regular A‐ and B‐DNA structures, whereas crystal structures of complexes with thio‐ and dithiophosphorylated oligonucleotides as substrate analogs show the importance of stacking and hydrogen‐bonding interactions with unpaired bases. These studies provide, in addition, a structural basis for the understanding of the low pH optimum of the enzyme and of its catalytic mechanism. This is most likely to be very similar to the three–metal ion mechanisms proposed forBacillus cereusphospholipase C andEscherichia coliendonuclease IV, although the latter enzyme has a completely different structure. In each case, the phosphate‐attacking nucleophile is a water or hydroxide molecule that is activated by two closely spaced zinc ions, assisted by hydrogen bonding to a nearby carboxylate group, and with stabilization of the leaving PO3′ anion by a third, more exposed zinc ion. Sequence comparisons with P1‐related nucleases confirm the importance of an invariant asparagine in the proper orientation of the substrate by hydrogen bonding to the O4′ atom of the ribose moiety that is situated next to the cleaved PO3′ bond.
Zinc Modules in Nuclear Hormone Receptors
Authors: Devarakonda Srikripa , Rastinejad Fraydoon 
Published: December 2011

AbstractNuclear hormone receptors are a family of transcription factors that modulate the transcription of target genes in response to their respective hormones. By activating expression of gene networks, they coordinate complex events involving development, differentiation, and response to diverse stimuli. Most receptors function as homo‐ or heterodimers and activate the target genes by binding selectively to regulatory sequences called DNA response elements (DRE) in the promoter region of the gene. The majority of members in this family recognize slight variations of the same consensus hexameric sequence – AGGTCA, through their DNA binding domains (DBD). The DREs contain the core hexameric sequence in various extended and bipartite configurations. The DBD consists of two zinc binding modules that fold onto each other to form a scaffold that is responsible for DNA binding and recognition. A series of three‐dimensional structures obtained from NMR and X‐ray crystallography have allowed the visualization of the DBDs alone and in their functional assemblies on the corresponding DREs. This chapter describes in detail the molecular and structural characteristics of the DBDs including their C‐terminal extensions as well as the topology of the various DREs that these receptors bind to. These features illustrate how a superfamily of receptors with highly conserved DNA binding domains can distinguish between closely related response elements. The structures described also indicate how cooperation between receptors enhances their joint affinity and selectivity for correctly configured sites.
LIM domain proteins
Authors: Kontaxis Georg , Bister Klaus , Konrat Robert 
Published: December 2011

AbstractLIM domain proteins are implicated in fundamental developmental processes, and the functional hallmark of all LIM domains is presumably the mediation of protein–protein interactions. Although originally identified in LIM‐homeodomain proteins, LIM domains have now been identified in a variety of proteins that lack homeodomains, either being entirely composed of LIM domains or containing additional functional domains of various types (e.g. kinase domains). The LIM domain contains a distinct cysteine‐rich motif that was first identified in the protein products of three genes –lin‐1,isl1, andmec‐3. The LIM motif is composed of two zinc finger structures separated by a two‐amino acid spacer and comprises the conserved sequence CX2CX16 − 23HX2CX2CX2CX16 − 21CX2(C/H/D).
Neprilysin
Authors: Dale Glenn E , Oefner Christian 
Published: December 2011

AbstractNeprilysin (NEP), a thermolysin‐like zinc metalloendopeptidase, is the major enzyme involved in the metabolic inactivation of a number of bioactive peptides including the enkephalins, substance P, endothelin, bradykinin, and the atrial natriuretic factor. NEP is an integral plasma membrane endopeptidase of the M13 family of zinc peptidases. Other related mammalian NEP‐like enzymes include the endothelin‐converting enzymes (ECE‐1 and ECE‐2), KELL and PEX. A number of novel mammalian homologues of NEP have also recently been described. Owing to the physiological importance of NEP in the modulation of nociceptive and pressor responses, there is considerable interest in inhibitors of this enzyme as novel analgesics and antihypertensive agents. Here we provide an overview of this pharmacologically important protein protease family.
Serralysin
Authors: Baumann Ulrich 
Published: December 2011

AbstractSerralysins (EC 3.4.24.40) are a family of 50‐kDa metalloproteases from gram‐negative enterobacteria. They are members of the metzincin clan of endopeptidases and possess the conserved zinc binding HEXXHXXGXXHP sequence motif, followed by a conserved methionine. The three‐dimensional structure shows that serralysins possess two domains; besides the typical metzincin‐protease domain that resides within the N‐terminal 220 amino acids, there is an extended C‐terminal β‐sheet domain. This domain contains six glycine‐rich tandem repeats GGXGXDXLX characteristic for the RTX‐toxin family. These repeats bind calcium ions.Recent studies include directed mutagenesis in order to clarify the function of the conserved methionine as well as the crystal‐structure determination of complexes between serralysins and their cognate inhibitors. The latter shows inhibition by a coordinative bond between the inhibitor's N‐terminus and the catalytic zinc ion.
Streptomyces AlbusGD‐Ala‐D‐Ala Carboxypeptidase
Authors: Charlier Paulette , Wery Jean‐Pierre , Dideberg Otto , Frère Jean‐Marie 
Published: December 2011

AbstractThe zincD‐Ala‐D‐Ala carboxypeptidase hydrolyzes the C‐terminal peptide bond of peptides of general structure R‐D‐Ala‐D‐Xaa. The lytic activity of the enzyme and its extracellular location suggest that it might be used byStreptomycesfor fighting competitors in its ecological niche since the enzyme does not hydrolyze theStreptomycespeptidoglycan.The sequence of the 213‐residue mature protein is related to the VanX, VanY, and VanXY proteins of vancomycin‐resistant enterococci. The molecule is an ellipsoid consisting of two globular domains in which the N‐terminal and the C‐terminal ends are pulled apart. The small N‐terminal domain, from residue Asp1 to Pro83, has an all‐α‐helices structure and exhibits a typical three‐helix bundle fold, characteristic of the peptidoglycan binding domain. The largest C‐terminal domain belongs to the α + β type secondary structure, and is related to the N‐terminal domain of the murine sonic hedgehog, a signaling protein involved in natal morphogenesis and formation of embryonic patterning centers, and to the VanXD‐Ala‐D‐Ala dipeptidase ofEnterococcus faecium, a protein involved in the vancomycin resistance systems in streptococci. The mixed five‐stranded β‐sheet forms the core of the C‐terminal domain and the lining of one side of the catalytic cavity. One zinc ion occupies a roughly central position in the active site and is coordinated by the His154 NE2, the Asp161 OD1, and the His197 ND1. Classical β‐lactam compounds, which readily inactivate active site serineDD‐peptidases, are very sluggish inactivators of the zincD‐Ala‐D‐Ala carboxypeptidase. The best competitive inhibitors are thiol derivatives such as 2‐ and 3‐mercaptopropionate (Ki = 50 and 5 nM) that might behave as bidentate ligands of the Zn2+ion.
Metallocarboxypeptidases
Authors: Vendrell Josep , Aviles Francesc X , Fricker Lloyd D 
Published: December 2011

AbstractMetallocarboxypeptidases (CP) catalyze the removal of C‐terminal amino acids from proteins and/or peptides. The different members of the CP family differ in their specificity for C‐terminal residues and physiological function and can be divided into two subfamilies. Members of the A/B subfamily are generally produced as proenzymes, contain an approximately 300‐residue CP catalytic domain, have greatest amino acid sequence identity to the exocrine pancreatic enzymes CPA and CPB, and prefer hydrophobic or basic residues. They function in the breakdown of peptides in food or in other physiological processes ranging from inflammation to fibrinolysis. Members of the N/E group cleave C‐terminal basic residues and are not produced as inactive proenzymes but contain an approximately 80‐residue region following the 300‐residue CP domain with structural homology to transthyretin. They act either extra‐ or intracellularly in the processing of peptide hormones and neurotransmitters and other physiologically relevant peptides.The tertiary folding of CPs corresponds to the α/β hydrolase fold and is formed by a central mixed parallel/antiparallel eight‐strand β‐sheet, with a 120° twist between the first and the last strand, over which eight α‐helices pack on both sides to form a globular molecule. All of the enzymatically active CPs bind one atom of Zn2+at the active site. Some members of the CP family that are inactive against standard CP substrates lack some of the cation‐binding ligands and may therefore not be able to bind the metal.
Leucine Aminopeptidase
Authors: Sträter Norbert , Lipscomb William N 
Published: December 2011

AbstractLeucine aminopeptidase belongs to the metallohydrolase family M17. In this family, two X‐ray diffraction structures are known for bovine lens LAP (blLAP) and for theEscherichia coliaminopeptidase A (PepA). These two peptidases are large homohexamers of 32 symmetry, and both have a large central solvent cavity near the active sites. Each active center contains two Zn2+separated by 3.0 Å. In PepA, maximal activity occurs in the presence of Mn2+. blLAP is activated by Mn2+, Mg2+or Co2+, but zinc is bound most strongly and is supposed to be the physiological cofactor. In the proposed catalytic mechanism, both metal ions stabilize substrate binding and formation of the transition state. In addition, a lysine side chain contributes by polarizing the substrate's carbonyl group, and an arginine side chain binds a bicarbonate anion (or carbonate ion) that is in a position to act, at least in PepA, as a general base to deprotonate the zinc‐bound water nucleophile.
5′‐Nucleotidase
Authors: Sträter Norbert 
Published: December 2011

Abstract

Escherichia coli

5′‐nucleotidase (5′‐NT) is a monomeric protein of 525 amino acids (58.1 kDa). The enzyme has a nutritional function in bacteria where it is exported to the periplasmic space to hydrolyze external nucleotides and UDP‐glucose. Related animal 5′‐nucleotidases are attached to the cell membrane via a GPI anchor and hydrolyze nucleotides as extracellular signaling substances.

E. coli

5′‐NT belongs to the calcineurin superfamily of metallophosphatases and contains two divalent metal ions at a distance of about 3.3 Å. One of these metal ions is probably Zn
2+
in vivo
. However, the Zn
2+
–Zn
2+
form is relatively inactive, whereas good activity is seen in the presence of Mg
2+
, Mn
2+
, and Co
2+
. The protein consists of two domains: a larger N‐terminal domain, which is related to the calcineurin superfamily and contains the two catalytic metal ions and its ligands, and the C‐terminal domain, which bears the substrate specificity pocket that binds the nucleoside moiety of the substrates. Thus, the active site is located at the interface between both domains. In the proposed catalytic mechanism, both metal ions are involved in substrate binding, activation of the nucleophile, and transition‐state stabilization. In addition, a catalytic histidine residue (His117 in

E. coli

5′‐NT) is strictly conserved in all enzymes of this superfamily.
Gating Domain of Calcium‐Activated Potassium Channel with Calcium and Calmodulin
Authors: Schumacher Maria A 
Published: December 2011

AbstractSmall conductance Ca2+‐activated K+channels (SK channels) are voltage‐independent and gated solely by increases in intracellular Ca2+such as that occurs during an action potential. SK channels are heteromeric complexes and consist of pore‐forming α‐subunits and calmodulin (CaM). CaM is constitutively associated with an intracellular region of the α‐subunit immediately C‐terminal to the pore, the CaM binding domain (CaMBD). In order to trigger channel opening, Ca2+must only bind the EF hands in the CaM N‐lobe. The 1.60‐Å crystal structure of the SK channel Ca2+/CaM/CaMBD complex reveals that the CaMBD forms an elongated dimer with a CaM bound at each end and each CaM wraps around three α‐helices, two from one CaMBD subunit and one from the other. The structure also provides a view of both Ca2+‐dependent and Ca2+‐independent protein interactions; only the CaM N‐lobe is calcified while the noncalcified C‐lobe is responsible for the CaM/CaMBD constitutive interaction. This structure combined with biochemical data suggests a possible gating mechanism in which Ca2+binding to each CaM N‐lobe exposes its hydrophobic patch, thus allowing it to interact with an adjacent CaMBD monomer. As each N‐lobe on adjacent monomers interacts with the other CaMBD C‐terminal region, a rotary force would be created between them and transmitted to the attached S6 pore helices in the gate region. In this chemo‐mechanical model, two CaMBD dimers would serve as mechanical levers to drive open the channel.
Calpain
Authors: Davies Peter L , Campbell Robert L , Moldoveanu Tudor 
Published: December 2011

AbstractCalpains are intracellular cysteine proteases that participate in Ca2+signaling. Some structural information is available for the ubiquitous mammalian isoforms m‐ and μ‐calpain. These 110‐kDa heterodimeric, multidomain enzymes differ in the level of Ca2+required for activation. A structural explanation for the Ca2+requirement is that the papain‐like active site is not assembled in the Ca2+‐free (apo) state. Moreover, the circular arrangement of domains appears to constrain the two protease core domains from assembling into an active conformation. Ca2+binding to the two penta–EF‐hand domains and to a C2‐like domain flanking the protease core may release these constraints. However, active site assembly requires the cooperative binding of Ca2+to two non–EF‐hand sites, one on each of the catalytic domains. These novel Ca2+binding sites appear to be an evolutionary addition to the papain‐like protease core. Thus, Ca2+acts at several different levels, at different sites, to tightly control the activity of this potent protease within the cell.
EHDomain
Authors: Overduin Michael , Ravi Kiran Mahadev 
Published: December 2011

AbstractThe Eps15 homology (EH) domain is a 100‐residue protein‐interaction module that consists of a pair of helix‐loop‐helix EF hand motifs. The second EF hand typically binds calcium tightly, providing structural stability. The EH domain is either found singly or in a series of two or three tandem repeats in a variety of eukaryotic proteins that are involved in endocytosis, vesicle transport, and signal transduction. Its function is to mediate interactions with Asn‐Pro‐Phe (NPF) sequences or related motifs that are also often repeated in ligand proteins. The structures, calcium coordination, and peptide binding modes of five monomeric EH domains have recently been elucidated, providing insights into their mechanisms of action.
Calcium‐Binding
EGF
‐Like Domains
Authors: Boswell Emma J , Kurniawan Nyoman D , Downing A Kristina 
Published: December 2011

Abstract

Epidermal growth factor‐like (EGF) domains are one of the more abundant modules found in functionally diverse extracellular proteins. The domain is characterized by six cysteine residues, which normally disulphide bond in a 1–3, 2–4, 5–6 pattern. A particular subset (cbEGF) contains the consensus sequence [DEQN]‐x‐[DEQN]
2
‐x

m

‐[DN]*‐x

n

‐[YF] (where
m
and
n
are variables and * indicates possible β‐hydroxylation) associated with the ability to bind calcium. At present, cbEGFs have three main functional roles, as a spacer unit, in protein–protein interactions, and in structural stabilization. High‐resolution structures of cbEGF domains have identified a common fold, comprising a major and a minor double‐stranded β‐hairpin, stabilized by the three consensus disulphide bonds. A single calcium ion binds to the amino terminus and is coordinated by a pentagonal bipyramidal arrangement of oxygen atoms. Each individual cbEGF domain contains a calcium‐binding site, whose affinity may be considerably enhanced by N‐terminal linkage to another domain. A number of inherited diseases caused by missense mutations within cbEGFs highlight the importance of the domain.
Gla‐Domain
Authors: Brown Mark A , Stenflo Johan 
Published: December 2011

AbstractThe term ‘Gla‐domain’ is used to describe the γ‐carboxyglutamic acid (Gla)‐containing region of certain vitamin K–dependent proteins such as prothrombin and factor IX. The domain comprises the first 45 or so amino acids at the N‐terminus of these proteins and contains 9–13 Gla residues that can bind divalent metal cations in a cooperative manner, the most physiologically important being Ca2+. Binding of Ca2+by the Gla residues induces a conformational transition in the domain that allows it to bind to phospholipid‐containing membranes, a requisite step for the biological functioning of the proteins. Gla residues are also found in two proteins of bone and the extracellular matrix (bone Gla protein or osteocalcin, and matrix Gla protein), and in neurotoxic peptides synthesized by molluscs of the genusConus, but these polypeptides are not considered to have a Gla‐domain as such, and will not be discussed here.
Calcium Pump (
ATPase
) of Sarcoplasmic Reticulum
Authors: Toyoshima Chikashi 
Published: December 2011

Abstract

Ca
2+
‐ATPase of sarcoplasmic reticulum is a membrane protein of 110 kDa and pumps Ca
2+
from the cytoplasm into the sarcoplasmic reticulum, an intracellular organelle, to relax muscle cells. Two Ca
2+
ions can be transported per ATP hydrolyzed and two or three protons are countertransported. The Ca
2+
‐binding sites are located side by side in the transmembrane region. The crystal structures of this ATPase obtained for Ca
2+
‐bound and unbound states show that large conformation changes take place during Ca
2+
binding and dissociation.
C
‐Type Animal Lectins
Authors: Weis William I 
Published: December 2011

Abstract

C‐type animal lectins are a large family of carbohydrate‐binding proteins, which display a strict dependence on Ca
2+
for their activity. Family members contain one or more carbohydrate‐recognition domains (CRDs) approximately 110 to 150 amino acids in length. Structural analysis of these proteins reveals that binding to sugars is mediated by direct coordination of a conserved Ca
2+
. The Ca
2+
dependence of sugar binding is exploited in a number of family members that serve as cell surface endocytic receptors, where the acidic environment of the endosome causes changes in Ca
2+
coordination and release of the bound ligand.
Hemopexin Domains
Authors: Xavier Gomis‐Rüth F 
Published: December 2011

AbstractThe mammalian serum glycoprotein hemopexin is engaged in the metabolism of heme and in the protection against oxidative stress. It is the lead structure of the hemopexin domains, which are made up of several hemopexin‐type repeats of about 40 residues. Such domains are also found as C‐terminal domains in matrix metalloproteinases, zinc‐dependent hydrolases belonging to the metzincin clan of metalloproteinases. In these proteases, they deal with protein–substrate and protein–inhibitor interactions and in activation events. Both protein classes have been characterized at three‐dimensional structural level. Moreover, hemopexin domains are present within vitronectins, extracellular matrix glycoproteins. In this case, similarity with the former has been just based on sequence information. The presence of hemopexin domains in hemopexins, vitronectins, and matrix metalloproteinases' C‐terminal domains suggests that these repeating peptide motifs have arisen by divergent evolution.
The Superfamily of Cadherins: Calcium‐Dependent Cell Adhesion Receptors
Authors: Ahrens Thomas , Stetefeld Jörg , Häussinger Daniel , Engel Jürgen 
Published: December 2011

AbstractSpecific cell–cell contacts are important in tissue morphogenesis, development, and during signal transduction of vertebrates as well as invertebrates. Cadherins are cell‐surface transmembrane receptors that mediate such specific, homotypic cell–cell adhesion. The adhesive activity of cadherins requires calcium binding by the ectodomain of the protein. The extracellular part of cadherins is composed of different numbers of individually folding cadherin repeats (CAD). Calcium binding pockets are located in the interdomain sections and conserved peptide sequences in consecutive domains are involved in coordination of three calcium ions per binding pocket. Low‐ and high‐affinity calcium binding sites have been detected and binding constants in the micromolar (Kd = 30–330 µM) to millimolar (Kd = 2 mM) range were determined. When calcium is added to purified cadherin ectodomains, rigidification and conformational changes are observed, exposing interaction surfaces that are involved in homoassociation of cadherins. This review summarizes electron micrographic, crystallographic, and recent NMR data analyzing the molecular details and functional consequences of calcium binding by cadherins.
Cytochromec2
Authors: Miki Kunio , Sogabe Satoshi 
Published: December 2011

AbstractCytochromec2participates in biological processes, such as respiration and photosynthesis in bacteria, and reacts with a variety of proteins by transferring electrons in the manner of both oxidants and reductants, as in the reaction with ubiquinol‐cytochrome c oxidoreductase (cytochrome bc1complex) and the photosynthetic reaction center. Cytochromec2is found in the periplasmic space of the membrane, both in non‐sulfur purple photosynthetic bacteria and in non‐photosynthetic bacteria and serves as the bacterial counterpart of mitochondrial cytochromec. The molecule of cytochromec2exhibits a roughly globular shape with axial dimensions of 25 × 25 × 35 Å. The polypeptide folding is mostly composed of five α‐helical elements and fairly extended loops connecting helices. The protein fold envelops the heme prosthetic group within a hydrophobic pocket.
Cytochromec551
Authors: Cutruzzolà Francesca , Arese Marzia , Brunori Maurizio 
Published: December 2011

AbstractFunctional ClassBiological FunctionAmino Acid Sequence InformationProtein Production, Purification and Molecular CharacterizationMetal Content and CofactorsSpectroscopy3DStructureFunctional AspectsSite‐Directed MutantsRelated Articles