bluuebunny/crossref_metadata_2025 huggingface dataset:
Methane–to–Methanol Conversion
Authors: Hashiguchi Brian G. , Hövelmann Claas H. , Bischof Steven M. , Lokare Kapil S. , Leung Chin Hin , Periana Roy A.
Published: December 2011

Natural gas (NG) is an abundant, clean, underutilized fossil fuel that can augment or replace petroleum as the feedstock to fuels and chemicals. However, given the relatively high transportation costs for this highly volatile gas, utilization of NG will only be possible if inexpensive, efficient, large‐scale technologies can be developed tochemicallyconvert NG to liquids feedstocks (e.g., long chain alkanes or methanol). Current syngas‐based technologies can carry out this chemical conversion with very high carbon yield (∼70%) while utilizing the only economically viable co‐reactant on this enormous scale: dioxygen or ideally air. However, despite these attractive characteristics, these processes are too expensive to displace petroleum primarily due to the high capital costs associated with the high temperatures required to generate syngas. Substantial effort toward the development of less expensive, lower temperature (<250 °C) processes for the selective, high‐yield oxidative conversion of methane, the major component of NG, to functionalized products has yielded a number of potential systems. This article is focused on one very promising approach: the use of homogenous organometallic and/or inorganic complexes in liquid solutions to mediate the oxidative conversion of methane. Heterogeneous (gas/solid) systems are not covered. Considering the ultimate goal of replacing petroleum with NG, we have organized this article with respect to both fundamental chemistry as well as the important practical considerations of whether or not systems can utilize dixoygen as the ultimate co‐reactant. Two fundamentally different mechanistic strategies have emerged: (i) the use of coordination catalysts that coordinate and cleave the CH bond of methane (defined as CH activation) or that coordinate and activate the co‐reactant (defined as oxidant activation), and (ii) the use of chain reactions based on reactive species such as free radicals or other chain carrying species. Systems that fall into these two categories are further categorized with respect to whether or not oxygen is or can be utilized as the ultimate co‐reactant. The goal is to provide the reader with an efficient way of quickly finding or classifying the rapidly growing body of literature by reaction mechanism and co‐reactant utilized.
Hydrogen Production from Water: Photocatalysis
Authors: Arachchige Shamindri M. , Brewer Karen J.
Published: December 2011

Photocatalytic hydrogen production from water provides an attractive but challenging approach to meeting our global energy needs. Design and development of systems that utilize visible light to drive the energetically favorable, multielectron reduction of water to produce hydrogen fuel have been of long‐term interest. Addressing the challenges of efficient harvesting of solar energy to produce transportable fuels requires ongoing, sustained research in this field. Current technologies utilize photobiological methods, photoelectrochemical methods, and molecular photocatalysis. This article focuses on the recent progress of proton or water reduction using supramolecular photocatalysts. These photochemical molecular devices often couple charge‐transfer light absorbers (LAs) to reactive metals in complex molecular architectures. Linking multiple components into large molecular assemblies allows for applications requiring complex functions. Early successes in supramolecular photocatalysts for solar hydrogen production are summarized. The redox, excited state properties, and photochemical properties of supramolecular systems applicable in photocatalytic hydrogen production are presented. Fundamental studies of the perturbations of subunit properties upon incorporation into supramolecular arrays are paramount to their successful application in this forum. Optical excitation typically affords a metal‐to‐ligand charge‐transfer state that is quenched by electron transfer, providing reduced complexes with reactive metals able to deliver the electrons to substrates. Sacrificial electron donors provide coupling to oxidative chemistry, allowing independent study of photocatalysts and hydrogen production schemes. Supramolecular chemistry allows modulation of redox, photophysical, and photochemical properties by component modification. Coupling multiple LAs to an electron acceptor, which, when reduced by multiple electrons, provides photoinitiated electron collectors (ECs). Photoinitiated ECs, which collect multiple electrons on a reactive rhodium center with the supramolecular architecture remaining, reduce water to hydrogen fuel. Mixed‐valence systems that promote HX reduction to produce hydrogen have also been described. Coupling of charge‐transfer LAs to cobalt, iron, palladium, or platinum is a topic of recent interest in the design of water reduction photocatalysts. The general design considerations for the development of supramolecular assemblies that function as photocatalysts for proton reduction are discussed, providing valuable insight into engineering efficient solar hydrogen production catalysts for water reduction. Mechanistic studies remain important to understanding this complex multielectron photochemistry, which will aid in future molecular design. Much remains to be mastered in this complicated, multielectron photochemistry but recently there is increased awareness and interest in this field.
Electrochemical and Photoelectrochemical Conversion of Carbondioxide to Alcohols
Authors: Crabtree Robert H.
Published: December 2011

Energy storage for intermittent alternative energy sources such as wind and solar could take the form of CO2reduction to liquid fuels, such as methanol. Electrochemical and photoelectrochemical methods are discussed.
Photosynthesis, Artificial: Progress in Swedish Consortium
Authors: Ott Sascha , Styring Stenbjörn , Hammarström Leif , Johansson Olof
Published: December 2011

Mimicking energy conversion processes in nature using molecular systems is a promising approach for future solar fuel production. The Swedish Consortium for Artificial Photosynthesis is involved in the design, preparation and functional study of many of the key components needed for a homogeneous approach to artificial photosynthesis, building on principles from photosystem II (PSII) and [FeFe] hydrogenases. Ruthenium(II) polypyridyl complexes have played an important role as photosensitizers. Several strategies have been developed for their preparation, and a novel approach to improve the photophysical properties of bistridentate complexes involving six‐membered chelates for more octahedral coordination was recently introduced. The [Ru(dqp)
2
]
2+
complexes (dqp is 2,6‐di(quinolin‐8‐yl)pyridine) combine the desired structural properties for easy access to linear donor–acceptor assemblies, while maintaining microsecond luminescent lifetimes of their
3
MLCT (metal‐to‐ligand charge transfer) excited states. The synthesis of these chromophores is now well established, and the recent realization of donor–photosensitizer–acceptor assemblies shows that photoproduced charge‐separated states can be formed in high yields (ϕ ≥ 95%). Beyond such single‐photon/single‐electron events, charge accumulation at potential catalytic sites is crucial for multielectron redox reactions. Covalently linked Ru
II
Mn

x

(
x
 = 1,2) complexes as PSII mimics have been investigated to understand chromophore–quencher (Mn quenchers) interactions, to promote desired electron transfer processes, and suppress undesired competing reactions. The Mn units often have large inner reorganization energies upon oxidation or reduction, which make them unusually slow electron donors and/or acceptors in photoinduced charge‐separation schemes. Charge accumulation and water splitting, however, require the management of
both
protons and electrons, which controls the electron transfer processes by proton‐coupled electron transfer (PCET). Studies on Ru
II
Tyr complexes incorporating pendant bases led to an understanding of the effect of hydrogen‐bonding on electron transfer rates. In analogy to the electron donor side, bioinorganic models of the [FeFe] H
2
ase active site are targeted for the electron acceptor side, with the ultimate goal to realize molecular catalysts that produce H
2
at similar high rates and low overpotential as the enzymes. Certain ligand sets create basic sites around the Fe centers that are protonated in the presence of acid and are thus models of late intermediates in the enzymatic catalytic cycle. Furthermore, synthetic Fe
2
complexes catalyze the electrochemical reduction of protons. In combination with a photosensitizer, they can also be used in photochemical schemes and are currently used to produce H
2
photochemically, with turnover rates up to 200.
Fuel Cells: Direct Ethanol
Authors: Chia Zhi Wen , Lee Jim Yang
Published: December 2011

Alcohols, and methanol in particular, have been investigated as potential fuels for use in direct fuel cells for mobile applications. However, the fuel cell community is now turning its attention to ethanol as the fuel of choice because of benefits such as renewability and low fuel toxicity. Nonetheless, the direct ethanol fuel cell (DEFC) has several technological problems that are more tenacious than the direct methanol fuel cell (DMFC). Among them, the slow anode kinetics presents the greatest challenge since it results in poor fuel cell performance in applications. Current anode catalysts, which are primarily an extension of the DMFC anode catalysts, do not prove to be very effective in delivering high current densities or sufficiently high conversions. Thus, there is a need to modify existing catalysts or to develop new catalysts that are able to oxidize ethanol molecules more effectively and more completely. This article provides a succinct account of the various catalysts currently in use at the anode and cathode of a DEFC, with emphasis on the anode catalysts used in an acidic environment, which require the most improvement. The use of cocatalysts, promoters, and catalyst support as well as catalysts used for ethanol oxidation in alkaline media are also briefly discussed.
Fuel Cells: Molecular Catalysis
Authors: Oyaizu Kenichi
Published: December 2011

Popularization of fuel cells has been impeded by the low activity of electrocatalysts for the O
2
reduction reaction that involves the four‐electron transfer step. Platinum nanoparticles have been considered the best cathode catalyst toward the reduction of O
2
by four electrons into H
2
O. However, platinum is an expensive and limited resource, and it is important to find platinum‐free catalysts. This article provides a review on the recent studies on various types of platinum‐free catalysts such as nonprecious metal nanoparticles and alloys, carbon‐based catalysts, and metal complexes, focusing on the role of structure of the catalytically active site of metal complex catalysts in the OO bond scission to produce H
2
O. Emphasis is placed on the studies on cobaltporphyrins, which have been demonstrated to serve as the catalysts for the four‐electron reduction of O
2
, especially in the forms of dicobalt cofacial porphyrins and multinuclear cobaltporphyrins. Simple metalloporphyrins with spontaneous face‐to‐face aggregation properties have also been examined as a catalyst. For practical application as fuel cell cathode catalysts, it is necessary to use metalloporphyrins dispersed on carbon particles with high surface area. We summarize the recent developments on porphyrin‐based catalysts and the attempts to prepare face‐to‐face aggregates of metalloporphyrins adsorbed dispersively on carbon black. A design principle for the active site to allow the O
2
reduction at positive potentials is proposed.
Photo–Initiated Electron–Transfer at the Interface between AnataseTiO2Nanocrystallites and Transition–Metal Polypyridyl Compounds: Recent Advances
Authors: Ardo Shane , Meyer Gerald J.
Published: December 2011

Molecular control of solar light harvesting and interfacial charge transfer at mesoporous, nanocrystalline semiconductor thin films are described. Light absorption by transition‐metal coordination compounds anchored to wide band‐gap semiconductors can initiate electron‐transfer processes that ultimately reduce the semiconductor and oxidize the coordination compound. Such photo‐induced charge separation is a key step for solar energy conversion. Three different interfacial charge‐separation mechanisms are discussed in addition to regeneration processes wherein a mobile donor donates an electron to the oxidized coordination compound. Inorganic chemistry plays a central role in this approach to solar energy conversion, which may ultimately be optimized for practical applications.
Zn‐Dependent Medium‐Chain Dehydrogenases/Reductases
Authors: Meijers Rob , Cedergren‐Zeppezauer Eila S
Published: December 2011

Medium‐chain dehydrogenases/reductases (MDRs) have about 350 to 390 amino acids and belong to a large superfamily of proteins including the Zn‐dependent alcohol dehydrogenases (ADHs) and several other Zn‐dependent activities. They are dimers or tetramers and utilize either NADH or NADPH as electron carriers referred to as cofactors. The oxidation/reduction process is a 2‐electron/1‐proton (hydride ion, H−) transfer between substrate and cofactor. The compounds oxidized or reduced by these enzymes vary considerably in structure ranging from small primary and secondary alcohols/aldehydes/ketones (aliphatic and aromatic), sugars (sorbitol/fructose, glucose) to large substances like fatty acids, steroids, and retinoids. ADHs are widely distributed in nature and some MDR members are found in all species. An essential Zn ion at the active site is common to all MDRs but some members have two zinc ions per subunit.

The 3D Structures of Zn‐dependent MDRs are highly similar and they essentially have the same polypeptide fold. The low sequence identity found sometimes could not immediately reveal this close structural relationship. Now numerous structures have been examined indicating that the evolutionary strategy for MDRs has been to vary amino acids preferably at the reaction center and further away in the substrate binding area. Thus, the size and shape of the substrate channel is adapted for small or large substrates, hydrophilic or hydrophobic substances, modifications attained via few mutations, or significant deletions/additions of amino acids. A further opportunity to create multiplicity has been to vary the control mechanism for the protein conformation change and the oligomeric state. Some enzymes undergo significant structural changes upon cofactor binding, while others do not.

A transition state intermediate of NADH in complex with horse liver alcohol dehydrogenase, resolved to atomic resolution (≈1 Å), has revealed structural modifications of the cofactor associated with the activation process for hydride transfer. This involves an OH−pyridine ring adduct, connected to the zinc center. The distortion of the nicotinamide at the enzyme site, affected by the presence of the negatively charged oxygen ligand, influences three parameters: (i) the puckering of the ring, (ii) a deviation from a standard carbon–carbon double bond length, and (iii) accumulation of negative charge at the C4 atom promoting hydride transfer. The active site Zn‐center of this large enzyme group shows great flexibility with respect to metal–ligand geometry and dynamics. Structural and spectroscopic evidence suggest that Zn‐dependent MDRs should be included in the general family of Zn‐enzymes, which require water and hydroxide ion as reactants during catalysis.
Carbonic Anhydrases (α‐Class)
Authors: Duda David M , McKenna Robert
Published: December 2011

Carbonic anhydrases (CAs) are zinc metalloenzymes that catalyze the hydration of carbon dioxide and the dehydration of bicarbonate:\catcode`@=11\newdimen\budimen\newbox\budbox\def\rrlh@#1{\vcenter{\parindent=0pt\hbox{\ooalign{\raise0.21em\hbox to 2pc{$#1\lhupfill$}\crcr$#1\rhdownfill$}}}}\def\lhupfill{\m@th\mathrel\leftharpoonup\mkern-6mu \cleaders\hbox{$\mkern-2mu\mathord-\mkern-2mu$}\hfill \mkern-6mu\mathrel-}\def\rhdownfill{\m@th\mathrel-\mkern-6mu \cleaders\hbox{$\mkern-2mu\mathord-\mkern-2mu$}\hfill \mkern-6mu\mathrel\rightharpoondown}\def\lrharpoonsfill{\vcenter{\parindent=0pt\ooalign{\raise0.21em\hbox to \budimen{$\lhupfill$}\crcr\hbox to \budimen{$\rhdownfill$}}}}\def\leftrighthfill#1{\mathrel{\lower0.1em\hbox{\ooalign{\raise0.21em\hbox to #1{$\lhupfill$}\crcr\hbox to #1{$\rhdownfill$}}}}}\catcode`@=12$\hbox{CO}_{2} +\hbox{H}_{2}\hbox{O}{\leftrighthfill{2pc}}\hbox{HCO}{_{3}}^{-} + \hbox{H}^{+}$, a process that has physiological importance in respiration, acid–base homeostasis, photosynthesis, and biosynthetic pathways. The α‐class of CA (and the CA domains in more complex isoforms) is monomeric with a molecular weight of approximately 30 kDa. At present, 14 isoforms of the α‐class are known with varying tissue distributions and catalytic activity. The catalytic turnover number of CAs varies from the maximal rate of 106s−1for isozyme II to 103s−1for isozyme III. The central structural motif of the α‐CAs can be described as a 10‐stranded twisted β‐sheet, which is flanked by seven α‐helices. The active‐site cavity consists of a single zinc ion tetrahedrally coordinated by three histidine residues (His94, 96, and 119) and a bound water molecule. In most of the α‐CAs, the resultant proton formed by the dehydration reaction of bicarbonate is transferred to bulk solution through the formation of a proton wire, mediated by residue His64, that lies at the mouth of the active site. Known inhibitors of CAs have been shown to bind to the metal ion and displace the zinc‐bound water, whereas activators have been shown to bind at the entrance of the active site and mimic the characteristics of the proton‐shuttling residue His64.
Carbonic Anhydrases (β‐Class)
Authors: Yamashita Eiki , Mitsuhashi Satoshi , Tsukihara Tomitake
Published: December 2011

Carbonic anhydrase (CA) catalyzes the reversible hydration of CO
2
to HCO
3
−
in aqueous solution. CAs are divided into three distinct classes (α‐CAs, β‐CAs, and γ‐CAs) that have little sequence homology to one another. β‐CA plays an essential role in photosynthesis, by concentrating CO
2
in the proximity of ribulose bisphosphate carboxylase/oxygenase for CO
2
fixation. Little is known about the physiological roles performed by β‐CA in nonphotosynthetic organisms.

Two homologous motifs are repeated in the

Porphyridium purpureum

β‐CA polypeptide (55 kDa). Each motif is composed of two components: an α/β domain and an N‐terminal arm. The two motifs in a monomer are related by a pseudo twofold axis. The two monomers form a dimer with pseudo 222 symmetry.

Escherichia coli

β‐CA and

Pisum sativum

β‐CA are composed of a tetramer and an octamer respectively. The dimer of

P. purpureum

β‐CA resembles a tetramer of

E. coli

β‐CA. A dimer of

P. sativum

β‐CA, which resembles the monomer of

P. purpureum

β‐CA, is the basic building block of the octamer.

Both β‐CAs from

Methanobacterium thermoautotrophicum

and

E. coli

have one zinc atom per monomer, while β‐CA from

P. purpureum

contains two zinc atoms per monomer. The catalytic zinc atom at each catalytic site is coordinated by four ligands in a tetrahedral manner. A possible catalytic mechanism of β‐CA based on the structure of

P. purpureum

CA is proposed.
GTPCyclohydrolaseI
Authors: Nar Herbert
Published: December 2011

GTP Cyclohydrolase I (GTP‐CH‐I) is a homodecameric protein complex of approximately 250 kDa molecular weight and it catalyzes the conversion of guanosine triphosphate (GTP) to dihydroneopterin triphosphate (H2NTP), the committing step in the biosynthesis of pteridines.

The GTP‐CH‐I monomer forms a compact single‐domain α + β structure containing a predominantly α‐helical N‐terminal subdomain and a sequential, four‐stranded, antiparallel β‐sheet in the C‐terminal subdomain. Association to dimers occurs along an antiparallel α‐helix pair. Decamers are formed by five dimers through the association of the respective four‐stranded, antiparallel β‐sheets to two 20‐stranded β‐barrel structures in each pentameric substructure of the active enzyme complex.

The active site is located at the interface of three monomers and is composed of a 12‐Å deep cavity that contains a guanine recognition motif at its bottom and a zinc binding site. The metal ion is coordinated by two cysteines and a histidine residue. A water molecule completes the coordination environment of the zinc in the resting state of the enzyme.

The role of the Zn(II) ion in catalysis is probably similar to its role in Zn(II)‐dependent proteinases and involves water activation in the guanine hydrolysis steps of the reaction sequence.

The product is formed by a subsequent Amadori rearrangement and ring closure. These steps involve acid–base catalysis and are probably performed by strictly conserved amino acid side chains in the vicinity of the zinc binding site.
Cocatalytic Zinc Sites
Authors: Auld David S
Published: December 2011

Cocatalytic zinc sites occur in enzymes where two or three metals are closely grouped to bring about catalysis. There are over four dozen representatives of this type of zinc site with the great majority belonging to the Class III hydrolases. A novel feature of these sites is the bridging of two of the metal sites by a side chain moiety of a single amino acid residue, such as the ring nitrogens of the imidazole group of histidine or the carboxylate oxygens of aspartic acid, glutamic acid, or of a carboxylated lysine, LysCO2−. Such an interaction requires the metals to be in close proximity to each other. The ligands to cocatalytic zinc sites often come from nearly the entire length of the protein, indicating that the metal sites may be important to the overall fold of the protein as well as to catalytic function. The secondary structure of the protein plays a major role in providing the ligands to these sites. In most cases, ligands are provided by amino acids residing within one or two residues before or after a β‐sheet or an α‐helix. The zinc ions are often penta‐coordinate and arranged in a trigonal bipyramidal geometry. The bridging amino acids and H2O probably have critical roles in catalysis. Their dissociation from either metal atom during catalysis will change the charge on the metal promoting its action as a Lewis acid or allowing interaction with an electronegative atom of the substrate. Thus, it can be envisioned for hydrolytic enzymes that substrate binding involves one zinc site acting as a template for substrate binding, while the other zinc site provides hydroxide for nucleophilic attack on the sp2center of the ester or amide bond of the substrate. In the next step, the roles of the metals can be reversed. In this manner, the metal atoms and their associated ligands play specific roles in each step of the reaction that works to bring about catalysis. The ligands in these sites, in particular the histidines, are often involved in further hydrogen‐bonding interactions with other amino acids. These interactions should effect the charge on the metal and the stability of the metal complex, thus fine‐tuning catalysis and the stability of the metal sites.
Metallothioneins
Authors: Zangger Klaus , Armitage Ian M
Published: December 2011

Metallothioneins (MTs) are small cysteine‐rich polypeptides that bind a series of metal ions and have been found in a variety of animals and even some plants. In animals, the different isoforms of MTs occur in tissues ranging from liver and kidney (isoforms 1 and 2) to the brain (isoform 3) and stratified epithelia (isoform 4). Today, the term metallothionein (MT) is used to denote ‘polypeptides resembling equine renal metallothionein in several of their features.’ On the basis of differing amino acid sequences and structural characteristics, MTs have been subdivided into three classes (I, II, and III), the first of which describes proteins with locations of cysteines closely related to those in equine renal metallothionein. Proteins with cysteine locations only distantly related to equine renal metallothionein are described in class II and atypical, nontranslationally synthesized metal‐thiolate polypeptides are contained in class III. Here we will focus on the structurally well‐characterized class I MTs, which bind zinc or its isomorphous metal‐ion substitute, cadmium. Specifically, these are MT2 from rabbit, rat, and human; MT1 from mouse, blue crab, and lobster; mouse MT3 and sea urchin MTA. In addition, the only structurally characterized class II zinc/cadmium‐containing MT, the cyanobacterial Smta will be discussed.

With the exception of the prokaryotic Smta, all these proteins show a dumbbell‐shaped two‐domain structure with six (blue crab and lobster MT1) or seven (all others) divalent metals bound in two separate metal–cysteine clusters. Although the exact physiological function of MTs is still not clear, a number of presumed functions have been put forward. In addition to the originally proposed dual role of MTs in zinc and copper homeostasis and heavy metal detoxification, they are also thought to be involved in the stress response to reactive oxygen species and possibly play a role at inflammatory sites as scavengers of nitric oxide.
RINGDomain Proteins
Authors: Dominguez Cyril , Folkers Gert E , Boelens Rolf
Published: December 2011

The RING domain is a cysteine‐rich sequence motif that can bind two zinc atoms. In the canonical RING motif, also called the C3HC4 motif, one zinc ion is bound to four cysteines, and the other ion to three cysteines and a histidine. The tetrahedral coordination is atypical and referred to as a ‘cross‐brace’ motif. There are now more than 380 RING motifs identified in the human genome. The RING domain has been shown to mediate a crucial step in the ubiquitination pathway that targets protein substrates for degradation by the 26 S proteasome. This pathway involves three enzymes, and the RING finger proteins have been classified in this scheme as ubiquitin ligases. There are actually nine structures of RING domains solved by X‐ray and NMR. The βαβ fold of the RING domain is conserved among all structures. The structures of RING domains in complex with other proteins involved in the ubiquitination pathway provide considerable insight into the molecular basis of ubiquitination. Recently, ubiquitination has been shown to be not only a simple protein removal system but also an indispensable regulatory process. This is underscored by the observation that many diseases, such as cancer and Parkinson's disease, are due to mutations in RING domains that prevent an efficient ubiquitination and degradation process. In this review, we compare the different structures of RING domains, analyze their functional aspects through structural information of RING domains in complex with other proteins, and describe medical aspects of RING finger proteins involved in cancer and Parkinson's disease.
FYVE
Domain
Authors: Kutateladze Tatiana G , Overduin Michael
Published: December 2011

The FYVE domain is a 65‐residue module that contains two tetrahedral zinc coordination centers. The zinc ions are bound by eight cysteine residues in a cross‐braced topology, providing structural stability. The FYVE domain is usually present as a single module or, more rarely, as a tandem repeat in eukaryotic proteins involved in a variety of biological processes including membrane trafficking and phosphoinositide metabolism. The biochemical function of the FYVE domain is the specific recognition of phosphatidylinositol 3‐phosphate [PtdIns(3)P], a phospholipid that is most concentrated in endocytic membranes. Structures, zinc coordination, and PtdIns(3)P binding modes of three FYVE domains have recently been characterized, providing mechanistic insights into their contributions to endocytosis, signal transduction, and cytoskeletal organization.
Thermolysin
Authors: Matthews Brian W
Published: December 2011

Thermolysin is a thermostable, zinc‐dependent endopeptidase. It is the prototypical member of the very large family of proteases characterized by the HEXXH sequence motif in which the two histidines coordinate the zinc ion and the glutamic acid is critical for catalysis.
Astacin
Authors: Stöcker Walter , Yiallouros Irene
Published: December 2011

The mono‐zinc endopeptidase astacin (EC 3.4.24.21) is a prototype for the astacin family and for the metzincin superfamily of metalloproteinases. Some astacins are digestive enzymes of invertebrates, but the majority serve functions during embryonic development, pattern formation, and epithelial differentiation throughout the animal kingdom. The catalytic protease domain of the astacins is topologically similar to the corresponding domains of the matrix metalloproteinases (MMPs), the adamalysins/reprolysins/ADAMs (a disintegrin and metalloprotease), the bacterial serralysins, and several other groups of zinc peptidases. They have in common a conserved zinc binding sequence, HEXXHXXGXXH, containing three histidines and a catalytically important glutamic acid residue, which acts as a general base during catalysis. Furthermore, there is a strictly conserved methionine‐containing turn structure beneath the active site, the Met‐turn, which gave rise to the designationmetzincinsfor this superfamily of metalloproteins. In astacin, in addition to the three histidine residues of the zinc binding motif, the metal is ligated by the Glu93‐bound ‘activated’ water and by Tyr149, positioned in the Met‐turn, resulting in a trigonal bipyramidal coordination sphere. This overview treats the structural basis for the function of astacin‐like proteases, including proenzyme activation, cleavage specificity, substrate and inhibitor kinetics, catalysis, and metal binding. It also pinpoints shared commonalities and subtle differences between astacin and other metzincins.
Matrix Metalloproteinases
Authors: Bode Wolfram , Maskos Klaus
Published: December 2011

The matrix metalloproteinases (MMPs) constitute a family of (in man) 23 different extracellular soluble/cell surface–anchored multidomain zinc endopeptidases, all of which exhibit a common catalytic domain of a metzincin‐like topology, that is, possess a Met‐containing tight turn and carry an extended His‐Glu‐Xaa‐Xaa‐His‐Xaa‐Xaa‐Gly‐Xaa‐Xaa‐His zinc‐binding consensus segment enwrapping the catalytic zinc, with the three histidine imidazole side chains and a nucleophilic water ligating the catalytic zinc, and the glutamine side chain presumably acting as a proton shuttle. The MMPs are involved not only in extracellular matrix degradation but also in a number of other biological processes such as shedding of membrane‐bound growth factor and cytokine precursors, pro‐proteinase activation, or inhibitor inactivation. Normally, their proteolytic activity is precisely regulated by endogenous protein inhibitors, in particular, by the tissue inhibitors of metalloproteinases (TIMPs). Disruption of this balance results in serious diseases such as arthritis, tumor growth, and metastasis, thus rendering the MMPs attractive targets for inhibition therapy. Individual vertebrate MMPs have been named according to their presumed substrates or classified by sequential (chronological) numbers, which run from MMPs 1 to 28. These MMPs are synthesized with an N‐terminal signal sequence, a pro‐domain, and a catalytic domain containing the catalytic zinc, a structural zinc, and up to three calcium ions. Additionally, most MMPs possess a C‐terminal ion containing hemopexin‐like domain, which, in the membrane‐bound MMPs, is followed by a transmembrane helix and a cytoplasmic domain, or a glycosil phosphatidyl inositol (GPI) anchor. This overview presents common and special structural features of the MMPs, in particular of their catalytic domain.
Bacillus SubtilisD‐AminopeptidaseDppA
Authors: Remaut Han , Goffin Colette , Frère Jean‐Marie , Beeumen Jozef Van
Published: December 2011

TheD‐aminopeptidase DppA, identified inBacillusspecies, represents the prototype of a separate family of dinuclear zinc proteases. The catalytic domain of the enzyme comprises a Rossmann‐like α/β/α‐fold that coordinates two zinc ions near the C‐terminal edge of a six‐stranded parallel β‐sheet. Despite the lack in sequence and structural homology, the zinc coordination is highly similar to that found in established dinuclear zinc proteases. Furthermore, DppA forms a decameric molecule that encloses a central cavity that sequesters the 10 active sites. The architecture of the complex strongly resembles that found in a group of enzymes known as self‐compartmentalizing proteases, with bacterial and eukaryotic proteasomes as most characteristic examples.
TroponinC
Authors: Gagné Stéphane M
Published: December 2011

Regulation of contraction in skeletal and cardiac muscle occurs through calcium binding to the protein troponin C (TnC). The N‐terminal domain of TnC (NTnC) carries out the regulatory role through the binding of calcium ions – two calcium ions in skeletal muscle and one in cardiac muscle.

Thirty‐nine sequences of TnC have been sequenced so far. Of the 39 sequences of TnC, 5 have had their three‐dimensional structures determined in various forms by NMR and X‐ray. Available structures include 26 uncomplexed structures in various calcium states, and 13 structures in which cardiac and skeletal TnC is complexed with fragments of troponin I and/or troponin T.
Parvalbumin
Authors: Nakayama Susumu , Kawasaki Hiroshi , Kretsinger Robert H
Published: December 2011

Parvalbumin was the first EF‐hand protein to have been characterized and to have its crystal structure determined. This prototype consists of an α‐helix E (extended forefinger of a clenched right hand), loop around the Ca
2+
ion (clenched middle finger), and α‐helix F (extended thumb). Parvalbumin has provided a reference point for the analyses of 76 other subfamilies of proteins that contain 2 to 12 EF‐hands. Most, but not all, EF‐hands bind calcium. The Ca
2+
ion is almost always coordinated by seven oxygen atoms arranged in an approximate pentagonal bipyramid; usually one of the ligands is a carboxylate group that coordinates calcium with both its oxygen atoms. The affinities of EF‐hands for calcium range from p
K
d
(Ca
2+
) 6 to 8. The dissociation constant of parvalbumin for calcium (
K
d
 ∼ 10
−8
 M) reflects one of the highest affinities of all the EF‐hand proteins. All, or most, of the EF‐hand proteins bind calcium ∼10
4.0
more strongly than they bind the six‐coordinate magnesium. Most of this difference in affinity derives from the ∼10
3.4
greater
on
rate for calcium, which in turn derives from its faster dehydration rate. Parvalbumin functions in fast, white, skeletal muscle to soak up messenger calcium following a stimulus, thereby facilitating rapid relaxation. Whether it has an analogous function in neurons, thymus, or other tissues remains to be demonstrated. Most EF‐hand proteins change conformation upon binding calcium, thereby transducing the information content of a pulse of cytosolic messenger Ca
2+
ions. Although the binding of calcium to the two EF‐hands of monomeric parvalbumin is not (or only very weakly) cooperative, as is the case for other EF‐hand proteins, the interaction of a pair of EF‐hands is essential for the stability of these proteins. The angle between the two helices (E and F) of a single EF‐hand as well as the contact between the pair of EF‐hands is usually more
open
following binding of calcium, thereby exposing hydrophobic side chains. However, a survey of the known structures of all known EF‐hands proteins does not reveal a bimodal
closed, open
set of conformations reflecting either binding of calcium and/or binding of targets for those EF‐hand proteins involved in information transduction.
PEFLINS: A Family of PentaEF‐Hand Proteins
Authors: Cygler Miroslaw
Published: December 2011

Penta‐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.
3DStructures of the Calcium and Zinc BindingS100 Proteins
Authors: Fritz Günter , Heizmann Claus W
Published: December 2011

S100 proteins are involved in many cellular processes such as cell growth and motility, cell cycle regulation, transcription, and differentiation. Twenty members have been discovered so far, and altogether, S100 proteins represent the largest subgroup within the EF‐hand Ca2+‐protein family. In resting cells, S100 proteins are localized in specific cellular compartments from which they relocate upon activation, hereby transducing the Ca2+/Zn2+signals by interacting with various target proteins. Some members are even secreted from cells exerting extracellular, cytokine‐like activities by interacting with the surface receptor RAGE.
Membrane BindingC2‐Like Domains
Authors: Verdaguer Nuria , Corbalán‐García Senena , Ochoa Wendy F , Gómez‐Fernández Juan Carmelo , Fita Ignacio
Published: December 2011

C2‐domains are independently folded modules, of about 130 residues, found in a large and diverse set of eukaryotic proteins. Many of the best‐characterized C2‐domains are found in proteins involved in membrane trafficking and fusion, such as synaptotagmins or rabphilin, and in signal transduction, such as phospholipases A2 (cPLA2) and C (PLC) or the protein kinase C isoforms (PKCs). All C2‐domains share a common overall fold: a single compact Greek‐key motif organized as an eight‐stranded antiparallel β‐sandwich consisting of a pair of four‐stranded β‐sheets – the A and B sheets – with a long axis of about 50 Å. Connections between β‐strands emerge from the top and bottom of the domain according to the two distinct topologies of C2‐domains. In topology I (the S family), the first β‐strand occupies the same structural position as the eighth β‐strand of topology II (the P family), which shifts in a circular permutation the order of homologous strands in the primary structure. The structural information defines adjacent calcium binding sites within a broad acidic cleft that contains highly conserved acidic residues. These provide most of the oxygen atoms that coordinate with the calcium ions. The present work will focus on the wealth of functional and structural information, which is being obtained at an exponential pace, on the membrane‐binding C2‐domains that require calcium.
Dockerin Domains
Authors: Volkman Brian F , Lytle Betsy L , David Wu J H
Published: December 2011

Bacterial protein domains known as dockerins serve as anchoring or tethering modules for the assembly of large extracellular cellulase complexes called cellulosomes. Dockerins function through interactions with another class of protein‐interaction module, the cohesins, and both domain families are currently divided into two subclasses (type I and type II) originally based on binding specificity. Dockerin sequences contain a pair of 22‐residue motifs with homology to calcium‐binding loops of the EF‐hand family. When exposed to calcium, the dockerin adopts a novel fold distinct from EF‐hand proteins that binds its cognate cohesin with high affinity. Conversely, in the absence of calcium, the dockerin domain is unfolded and does not bind cohesin. Thus, dockerin domains serve as calcium‐regulated mediators of protein complex formation. Analysis of conserved sequence features in the context of the three‐dimensional dockerin structure may identify elements that confer class and species specificity of dockerin–cohesin binding reactions.
PhospholipaseA2
Authors: Betzel Christian , Singh Tej P , Georgieva Dessislava , Genov Nicolay
Published: December 2011

Phospholipase A2s (phosphatidesn‐2 acylhydrolase, EC 3.1.1.4, PLA2) hydrolyze specifically thesn‐2 ester bond of phospholipids (PL). With some exceptions, they are Ca2+‐dependent enzymes. PLA2s are present in many organs and body fluids of vertebrates, invertebrates, and insects. They play an important role in the phospholipid digestion, remodeling, and metabolism, and are involved in human diseases such as acute pancreatitis, rheumatoid arthritis, respiratory distress, and acute chest syndrome. This review summarizes recent data on the biological function, amino acid sequence, classification, structure–function relationships, and 3D structures of PLA2s. Special attention is paid to the pharmacological activities of the snake venom enzymes. These hydrolases exert their activity through specific protein–protein interactions. Two types of structurally and functionally distinct receptors, N‐ and M‐type, were identified during the last decade and characterized. PLA2binding to its protein receptor can lead to cell damage, tissue necrosis, and other undesirable processes. The ‘interfacial activation’ of the enzymes and their participation in the interfacial catalysis are discussed. Protection of cell membranes from PLA2s is of medical importance.
Calsequestrin
Authors: Kang ChulHee
Published: December 2011

The contraction/relaxation of the muscle cell is controlled by the transient increase/decrease of Ca2+concentration. A large fraction of this Ca2+is stored in and released from the sarcoplasmic reticulum (SR) by the presence of high concentrations of an acidic protein, calsequestrin, in the lumen of the junctional terminal cisternae of SR. Calsequestrin binds and releases large quantities of Ca2+ion rapidly: about 40 to 50 ions per molecule with a binding constant of approximately 1 mM under physiological conditions. The cation binding by calsequestrin is nonspecific and the Ca2+binding sites incorporate the numerous acidic residues that comprise over one‐third of the total residues. The crystal structure of calsequestrin shows that it is made up of three domains, each with a thioredoxin fold. Ca2+ions are bound on the protein surface and between domains. Two distinct dimerization contacts in calsequestrin crystals suggested a mechanism for Ca2+regulation resulting from the occurrence of coupled Ca2+binding and protein polymerization. Ca2+‐induced formation of one contact was proposed to lead to dimerization followed by Ca2+‐induced formation of the second contact to bring about polymerization. Strong cooperative calcium binding accompanies the polymerization of calsequestrin into insoluble, extended, and often needle‐like structures. The polymerization of calsequestrin also provides a highly charged surface onto which calcium is adsorbed. A sparingly soluble ion such as Ca2+would tend to spread over the surface of the polymer, forming a readily exchangeable film. The propensity of Ca2+‐bound calsequestrin to form linear structures would make Ca2+dissociation and diffusion a more rapid event.
Myoglobin
Authors: Phillips George N
Published: December 2011

Functional Class

Occurrence

Biological Function

Amino Acid Sequence Information

Protein Production, Purification and Molecular Characterization

Metal Content and Cofactors

Activity Test

Structural Studies

Structural Basis of Reversible Oxygen Binding

Spectroscopic Studies on Myoglobin

Other Structural Studies on Myoglobin

Folding/Unfolding of Myoglobin

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Authors: Soriano Glenda M , Smith Janet L , Cramer William A
Published: December 2011

Cytochromef(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.
Cytochromecd1Nitrite Reductase
Authors: Allen James WA , Ferguson Stuart J , Fülöp Vilmos
Published: December 2011

Cytochromecd1catalyzes the one‐electron reduction of nitrite (NO2−) to nitric oxide and water. It is isolated from many bacteria, which respire by the process of denitrification.In vitro,cd1is also an oxidase and a hydroxylamine reductase. Each monomer of the dimeric enzyme contains onec‐type cytochrome center, which accepts electrons from donor proteins, and oned1heme, which is the active site and is unique to this class of enzymes. High‐resolution X‐ray structures have shown that in the oxidized forms, when isolated, the axial coordination of the hemes differs between the best‐studied cytochromescd1, the enzymes fromParacoccus pantotrophusandPseudomonas aeruginosa. Upon reduction, theP. pantotrophusenzyme undergoes a major and unprecedented conformational change and adopts the same heme coordinations as that of the reducedP. aeruginosacd1. The structural differences between the enzymes from these two sources are reflected in their biochemical, electron transfer, and spectroscopic properties.