bluuebunny/crossref_metadata_2025_split huggingface dataset:
PEFLINS: A Family of PentaEF‐Hand Proteins
Authors: Cygler Miroslaw 
Published: April 2006

AbstractPenta‐EF hand proteins, or PEFLINs, belong to the superfamily of regulatory Ca2+‐binding proteins with EF‐hand motifs. The calcium‐binding domain is ∼170 residues long and contains five EF‐hand motifs, of which only some retain the ability to bind calcium. Within individual molecules the (1st + 2nd) and (3rd + 4th) EF‐hands are associated in pairs while the 5th EF‐hand is unpaired. This domain is associated with an N‐terminal domain of varying length, usually 20 to 100 residues long and with a Gly/Pro‐rich region. Binding of Ca2+promotes association of these proteins with membranes, andin vitroleads to aggregation. On the basis of the 1st EF‐hand, these proteins are divided into two subfamilies. Calpain, grancalcin, and sorcin have a one‐residue deletion in the Ca2+‐binding loop between helices E and F and form a distinct variant of calcium binding. ALG‐2 and peflin have the canonical EF1 hand and bind calcium in a standard way. All penta‐EF hand proteins form homo‐ or heterodimers. The dimerization is promoted by pairing of the 5th EF‐hand of each molecule; thus in the dimer all EF‐hands are paired. Binding of Ca2+promotes only small, mostly local, conformational changes and it is plausible that binding of a concomitant partner molecule is required for larger rearrangements to occur.
Calcium‐Binding
EGF
‐Like Domains
Authors: Boswell Emma J , Kurniawan Nyoman D , Downing A Kristina 
Published: April 2006

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.
Annexins: Calcium Binding Proteins with Unusual Binding Sites
Authors: Rosengarth Anja , Luecke Hartmut 
Published: April 2006

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.
Calcium Pump (
ATPase
) of Sarcoplasmic Reticulum
Authors: Toyoshima Chikashi 
Published: April 2006

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: April 2006

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: April 2006

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.
C
2‐Domain Proteins Involved in Membrane Traffic
Authors: Rizo Josep 
Published: April 2006

Abstract

C
2
‐domains are the second‐most abundant Ca
2+
‐binding modules in nature. Their most common activity is Ca
2+
‐dependent phospholipid binding, but other types of interactions have been observed for these versatile protein modules. A variety of proteins involved in membrane traffic contain multiple C
2
‐domains, which often appear as two tandem C
2
‐domains as in the case of synaptotagmins and rabphilin. The structures of the C
2
‐domains of these proteins consist of a conserved β‐sandwich, formed by two four‐stranded β‐sheets, with variable loops at the top and the bottom that sometimes contain α‐helices. Multiple Ca
2+
‐ions bind in a tight cluster at the top loops, usually without inducing substantial conformational changes. Instead, electrostatic changes caused by Ca
2+
binding induce the Ca
2+
‐dependent interactions of C
2
‐domains, which can also be aided by hydrophobic interactions and partial coordination of Ca
2+
by the target molecules. Extensive analysis of the structure and Ca
2+
‐binding properties of the two synaptotagmin 1 C
2
‐domains has helped design genetic experiments that have strongly supported the notion that this protein acts as the major Ca
2+
sensor in neurotransmitter release. These studies have also suggested that Ca
2+
‐dependent phospholipid binding underlies the function of synaptotagmin 1 in triggering release.
Metal‐Dependent TypeIIRestriction Endonucleases
Authors: Vanamee Éva Scheuring , Aggarwal Aneel K 
Published: April 2006

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.
Cytochromec2
Authors: Miki Kunio , Sogabe Satoshi 
Published: April 2006

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.
Cytochrome

c

6
Authors: Reuter Wolfgang , Wiegand Georg 
Published: April 2006

Abstract

Cytochrome
c
6
, or its functional analog copper protein plastocyanin, mediates the intrathylakoidal photosynthetic electron transfer from the always dimeric cytochrome
b
6
f
complex to the monomeric and/or trimeric Photosystem I (PS I) complex. The high‐potential monoheme protein belongs to the omnipresent cytochrome
c
family and is mainly characterized by its highly conserved N‐terminal heme coordinating sequence C–X–X–C–H and a low spin heme‐iron with methionine and histidine as axial ligands. Despite the excellent knowledge about synthesis, structures, and physical properties of cytochrome
c
6
from various organisms, the real molecular events that occur during its reduction by cytochrome
b
6
f
and its oxidation by the reaction center of PS I are presently uncertain. In addition, the specific role of cytochrome
c
6
within the hydrogen metabolism in an anaerobic environment is in the focus of interest. However, the presentation of established information about cytochrome
c
6
is accompanied by a brief discussion on the biochemical and physiological aspects concerning function, association, and changes of the molecule.
Cytochrome

c

4
Authors: Andersen Niels H , Christensen Hans EM , Iversen Gitte , Nørgaard Allan , Scharnagl Christina , Thuesen Marianne H , Ulstrup Jens 
Published: April 2006

Abstract

The di‐heme
c
‐type cytochrome
c
4
has been identified in the membrane space of a number of bacterial species, and the isolation and sequencing have been reported. The biological role is believed to be part of a respiratory chain. Recombinant cyt
c
4
from
Pseudomonas stutzeri
(190 residues) has become available since the publication of the chapter.

The 2.2 Å crystal structure has disclosed two almost equally sized globular domains, each with a His/Met axially coordinated heme group. Variable degrees of two‐fold structural symmetry can be distinguished. The relative heme group orientation is tilted with a short (2.6 Å) hydrogen bond between the propionate in each heme. The protein is strongly dipolar, with excess negative and positive charges of the N‐ and C‐terminal domains, respectively. UV/vis, nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and resonance Raman spectral data point to distinct electronic features of the heme groups. The oxidized N‐terminal heme is in a mixed high‐spin/low‐spin state, while the reduced N‐terminal heme and both oxidized and reduced C‐terminal heme are in a pure low‐spin state. Chemically induced sequential unfolding of the domains also reflects selective domain properties.

As a two‐centre redox metalloprotein, cyt
c
4
offers a prototype case for mechanistic mapping of a multi‐centre redox protein. Electron transfer between cyt
c
4
and small reaction partners is multi‐phasic but the role of intramolecular electron transfer is inconclusive. Electrochemical electron transfer at low ionic strength, however, seems to involve unidirectional oxidation or reduction of the heme groups via intramolecular electron transfer. This may carry over to
in vivo
cyt
c
4
function in membrane environments.
Cytochromef
Authors: Soriano Glenda M , Smith Janet L , Cramer William A 
Published: April 2006

AbstractCytochromef(f, folium, leaf), ac‐type cytochrome with a characteristic CysXXCysHis amino acid sequence for heme ligation, is the largest of the four major protein subunits of the membrane‐embedded cytochromeb6fcomplex of oxygenic photosynthesis. It contains 285–86 amino acids, consisting of a soluble 250‐residue domain on the p‐side (positive‐side) or lumen‐side of the membrane, a single trans‐membrane 20‐residue α‐helix, and an n‐ or stromal‐side segment consisting of 15 residues. These domains contain, respectively, the heme prosthetic group and intraprotein electron transfer pathway, the membrane anchor and a short segment that is important in the assembly of theb6fcomplex.The function of the cytochromefin oxygenic photosynthesis is to act as the terminal electron acceptor in the membrane‐embedded cytochromeb6fcomplex that provides the electron transport connection between the photosystem II and photosystem I reaction centers. Electron transfer through the complex is coupled to proton translocation and generation of a proton electrochemical potential that is utilized to drive the synthesis of ATP through the proton‐motive ATP synthase.These functions of the cytochromeb6fcomplex are analogous to those of the multisubunit cytochromebc1complex (ubiquinol:cytochromecoxidoreductase) of the mitochondrial respiratory chain and photosynthetic bacteria. Both complexes contain four redox centers with very similar redox and structural properties: a covalently boundc‐type heme in cytochromeforc1, the 2Fe–2S cluster of the Rieske ISP, and the two noncovalently bound hemes of cytochromeb. The structure properties have been defined in 3.0–3.1 Å structures of theb6fcomplex from a thermophilic cyanobacterium and a green alga. These structures also defined a fifth redox prosthetic group, a novel covalently bound heme, tentatively called hemex. With the exception of the extrinsic cytochromesfandc1that, except for the heme‐binding peptide sequence, are completely different, the redox‐active protein subunits of thebc1andb6fcomplexes are structurally similar. For theb6fcomplex, structures at the level of atomic resolution (<2 Å) have also been obtained for the p‐side or lumen‐side extrinsic domains of cytochromefand the Rieske high potential [2Fe–2S] protein, which together constitute approximately 40% of the total mass of the complex.
Cytochromef/Plastocyanin Complex
Authors: Ubbink M 
Published: April 2006

AbstractIn the photosynthetic electron transfer chain in plants, cytochromef, a subunit of the cytochromeb6fcomplex, acts as electron donor for plastocyanin. Plastocyanin is a small soluble protein, which shuttles electrons to photosystem 1. The structure of the short‐lived and weak complex of the soluble domain of cytochromefand plastocyanin has been determined using nuclear magnetic resonance. It shows that the heme iron of cytochromefand the copper ion of plastocyanin are in close proximity, enabling fast electron transfer. The copper ligand His87 is located close to the iron ligand Tyr1, suggesting that electron transfer occurs via the hydrophobic patch of plastocyanin. Electrostatic interactions are also important in the complex. These findings are discussed in the light of studies of the electron transfer kinetics.
Chloroperoxidase
Authors: Sundaramoorthy Munirathinam 
Published: April 2006

AbstractChloroperoxidase (CPO) secreted by the marine fungusCaldariomyces fumagocatalyzes the formation of carbon–halide bond between the halide (I–, Br–, or Cl–) and the acceptor substrate. It is the most versatile of the heme (iron porphyrin) enzymes catalyzing four distinct reactionsin vitro, namely, (a) halogenation (haloperoxidase), (b) dehydrogenation (peroxidase), (c) peroxide dismutation (catalase), and (d) mono‐oxygenation (cytochrome P450). CPO is also unique in its structure with a novel tertiary fold, a P450‐like proximal thiolate ligand (Cys29) to heme iron, a peroxidase‐like distal charged residue (Glu183), and extensive glycosylation. This review describes the natural occurrence of CPO, its purification, structural and functional aspects of the native enzyme, enzyme‐intermediates and enzyme‐ligand derivatives characterized by X‐ray crystallography and various spectroscopic methods. The mechanism for the CPO catalytic cycle explaining its diverse functions and the role of the distal residue Glu183 is provided.
Hydroxylamine Oxidoreductase
Authors: Igarashi Noriyuki , Tanaka Nobuo 
Published: April 2006

AbstractAmmonium oxidizing bacteria acquire their growth energy by oxidizing ammonia to nitrate. Hydroxylamine oxidoreductase (HAO), a periplasmic multi‐heme enzyme, shoulders the central role of this respiratory system by catalyzing the four‐electron oxidation from hydroxylamine to nitrite. Spectroscopic, catalytic, and crystallographic studies on HAO have been performed in detail for many years. The crystal structure of HAO fromNitrosomonas europaeashowed that the molecule is a homotrimer containing a total of 24 hemes, which form a branched chain. The structure also revealed a unique catalytic center known as heme P460, and suggested the plausible sites of cytochrome binding on the molecular surface.
Heme‐Catalases
Authors: Maté Maria J , Murshudov Garib , Bravo Jerónimo , Melik‐Adamyan William , Loewen Peter C , Fita Ignacio 
Published: April 2006

Abstract
The mono‐functional heme‐containing catalases are tetrameric enzymes, ubiquitous in aerobic organisms, specialized in the “catalatic” reaction – the dismutation of hydrogen peroxide to oxygen and water. For these enzymes two well‐defined subgroups can be defined according to the length of their polypeptide subunits of about either 500 or 700 residues, respectively. All the enzymes present a strikingly high structural similarity for about 450 residues that define the “catalase fold” with larger catalases containing an extra “flavodoxin‐like” C‐terminal domain. Catalysis, though centered around the heme iron atom, requires the critical contribution of long and intricate molecular channels.
Rubredoxin
Authors: Meyer Jacques , Moulis Jean‐Marc 
Published: April 2006

AbstractRubredoxins are small (45–55 amino acids) proteins containing a single iron ion tetrahedrally coordinated to the sulfur atoms of four cysteine residues occurring in two symmetry‐related Cys‐x‐x‐Cys‐Gly loops. The structure and redox properties of rubredoxins have been analyzed in considerable detail by X‐ray (at atomic resolution) and neutron crystallography, optical spectroscopies, NMR, various other magnetic spectroscopies, and molecular engineering. Variations of the canonical rubredoxin structure include lengthening (Cys‐x‐x‐x‐x‐Cys) or shortening (Cys–Cys) of one of the ligand loops, as well as its integration in larger proteins containing more than one metal site. Rubredoxins are found in a wide range of Archaea and Bacteria, but only exceptionally in Eukarya. They function as electron transfer agents in various redox processes, many of which remain to be fully characterized.
The [2
Fe
–2
S
] Ferredoxins
Authors: Zanetti Giuliana , Binda Claudia , Aliverti Alessandro 
Published: April 2006

Abstract

The 2Fe ferredoxins (Fds) are simple iron–sulfur proteins, containing one 2Fe–2S cluster, that are involved mainly as electron carriers of low oxidation–reduction potential in fundamental metabolic processes. They can be subdivided into three families: class I, plant‐type; class II, adrenodoxin‐type; and class III,
Clostridium
‐type; according to the spacing in the sequence of the cysteinyl residues that bind the iron atoms of the cluster. All the Fds are monomers of 11–14 kDa, except for class III Fds that are dimer, with one cluster per subunit.

The cluster of 2Fe Fds contains two atoms of iron, bridged by two acid‐labile inorganic sulfide atoms, and coordinated to four cysteinyl sulfurs of the polypeptide chain. Fds absorb light in the 300–500 nm visible region, mainly due to sulfur‐Fe
3+
charge‐transfer transitions. The cluster in the oxidized protein contains two antiferromagnetically coupled, high‐spin (S = 5/2) ferric irons and is, therefore, electron paramagnetic resonance (EPR) silent. Upon one‐electron reduction, Fds become paramagnetic.

The three‐dimensional (3D) structure of several 2Fe Fds have been obtained either by X‐ray crystallography or by n
uclear magnetic
resonance (NMR) spectroscopy. The solution structures are very similar to the 3D crystal structures. The protein structure motif characteristic of Fds has been named β‐grasp – a five‐stranded antiparallel β‐sheet with an α‐helix lying on top of the sheet. This central core (β1–β5 and α1) is surrounded by two short β‐strands, an α‐helix (α2), and a short C‐terminal helical turn (α3). Class II Fds have an additional interaction domain. Comparison of the structures of the different proteins reveals conformational differences especially between class I and II ferredoxins. The binuclear iron cluster lies in a solvent‐exposed pocket generated by the loop connecting helix α1 and strand β3 and comprising three of the cysteinyl ligands. This loop is anchored through several hydrogen bonds to different parts of the protein molecule. An extensive survey of the literature on the interactions of several 2Fe Fds with their respective partners is presented.
Ferredoxins Containing Two DifferentFe/SCenters of the Forms [4Fe–4S] and [3Fe–4S]
Authors: Stout Charles D 
Published: April 2006

AbstractThis article reviews 7Fe ferredoxins (Fds), [FeS] proteins that contain [3Fe–4S]+/0and [4Fe–4S]2+/+clusters. The 7Fe Fds from 19 prokaryotes are described in terms of biological function, and categorized with respect to cysteine ligand motifs, length of amino‐acid sequence, and metal ion content. Biochemical, mutagenesis, electrochemical, spectroscopic, and crystallographic data are summarized for well‐studied examples of distinct subclasses, including 7Fe Fds fromAzotobacter vinelandii,Desulfovibrio africanus,Bacillus schlegelii, andSulfolobus acidocaldarius. 7Fe Fds have been used to study cysteine ligand motifs, the interconversion of [3Fe–4S] and [4Fe–4S] clusters, proton transfer to [3Fe–4S]0clusters, and the protein control of [FeS] cluster reduction potential.