bluuebunny/crossref_metadata_2025 huggingface dataset:
Lead: Radionuclides
Authors: Sabuti Asnor Azrin , Rahim Mohamed Che Abd
Published: December 2011

Lead (Pb) is a highly toxic and radiogenic metal. It occurs naturally in the Earth, but is not very abundant. Even so, lead isotopes have been very useful ss tracers in glaciology, limnology, oceanography, and in atmospheric studies of global (transboundary) and local pollution. The dominant radioisotope of lead is210Pb, a very ubiquitous secondary radionuclide that is formed from238U decay via222Rn.210Pb originates from the Earth's crust, through the decay of226Ra. There are many factors that complicate the behavior of210Pb in soil, air, and water. Owing to these, a great deal of effort has been devoted to the quantitative determination of lead isotopes over the past few years. The separation and counting techniques for lead need to be rapid, convenient, and precise, and utilize very small amounts of material. Humans are exposed to lead through ingestion and inhalation, and it is stored for long periods of time mainly in bone and teeth. Thus, more studies on environmental exposures to lead need to be conducted, particularly for air monitoring, dust, water, and soil sampling, and lead‐based product sampling.
Technetium: Radionuclides
Authors: Hu Qinhong
Published: December 2011

This article provides a review of Tc with regards to the basic chemistry, occurrence, speciation, separation, analysis, fate, and transport. Environmental99Tc originates from the nuclear fuel cycle, with most of the isotope (>90%) discharged from reprocessing plants in Europe. It has been recognized that99Tc is a very important dose contributor in risk assessment, because of its high abundance, long half‐lives, and presumably high mobility. Essentially all the technetium on the Earth has been created by human activities involving fissionable materials. Among 11 metastates of technetium,97mTc is the most stable, with a half‐life of 90.1 days. The common oxidation states of technetium include 0, +2, +4, +5, +6, and +7. Depending upon the redox conditions, Tc primarily exists in two (+7 and +4) stable oxidation states in the subsurface. Under oxidizing conditions, technetium (VII) will exist as the mobile pertechnetate ion (TcO4−) in aqueous solution. Reduction of TcO4−to Tc(IV) species (TcO2 · nH2O) will decrease Tc mobility, because Tc(IV) species are strongly retarded from mineral sorption and/or precipitation. ICP‐MS is the common analytical method used to quantify Tc levels.
Europium: Radionuclides
Authors: Wang Xiangke , Li Jiaxing
Published: December 2011

The physicochemical behavior of europium in the environment and the speciation of europium under different experimental conditions are described. The behavior and speciation of Eu(III) in the environment are dominated by the surface properties of solid particles, presence of natural organic and inorganic materials, pH values of the systems, and other parameters. Europium can be characterized and analyzed by spectrophotometry, polarography, atomic adsorption spectrometry (AAS), atomic emission spectrometry (AES), atomic fluorescence spectrometry (AFS), atom mass spectrometry (AMS), X‐ray fluorescence spectrometry (XFS), neutron activation analysis (NAA), and liquid scintillation counting (LSC).
A
tlantic
O
cean: Radionuclides
Authors: Kershaw Peter
Published: December 2011

This article summarizes the main sources and the fate of radionuclides in the Atlantic Ocean, resulting primarily from human activity. This covers direct and indirect sources of artificial radionuclides due to global fallout from weapons testing, controlled releases from nuclear establishments, the deliberate disposal of radioactive waste, accidental inputs, and the presence of naturally occurring radionuclides, sometimes in enhanced quantities due to human activities. The distribution and behavior of radionuclides in seawater, sediments, and biota are described, being a consequence of both the nature of the source term and the fundamental properties of the radionuclides (chemical behavior, half‐life). Finally, the article considers the radiological consequences due to the principal sources responsible for the maximum dose to the human population: nuclear fuel reprocessing and naturally occurring radionuclides.
Mediterranean Sea: Radionuclides
Authors: Delfanti Roberta , Papucci Carlo
Published: December 2011

The main sources of anthropogenic radioactivity in the Mediterranean Sea are fallout from atmospheric nuclear weapon testing and from the Chernobyl accident in 1986, while the releases from the nuclear industry are small. Consequently, the present radionuclide levels in the marine environment are of no concern from the radiological point of view. However, the Mediterranean Sea is an ideal environment to show how both coastal and open‐sea processes act to redistribute radionuclides in the different compartments of the marine environment. In fact, the Mediterranean Sea is considered a miniature ocean, where all the processes characterizing the global ocean take place on smaller space and timescales. For these reasons, in the past decades it had largely been used as a “laboratory basin” for process studies. In this framework, anthropogenic and natural radionuclides were often measured to be used as tracers of water mass dynamics, transit and renewal times, particle dynamics, sediment accumulation, etc. In this article, we first briefly describe the physical and biogeochemical characteristics of the Mediterranean Sea. After reviewing and quantifying the sources of radioactivity, we mainly focus on two radionuclides: (i)137Cs: conservative in the open sea, the most abundant anthropogenic radionuclide, and, among these, the main contributor to radioactive dose to the population, and (ii) the very long‐lived239,240Pu: nonconservative and the most abundant among transuranics. We describe their distribution and time trend in seawater, sediments, and biota, define their budgets in the basin, quantify the exchanges at the Gibraltar and Turkish Straits, and indicate future trends. We also report levels and distributions of selected natural radionuclides: (i)238U, with234Th as the main tracer for particle dynamics and whose concentration in the Mediterranean slightly differs from that in the oceans, and (ii)210Po, which is efficiently accumulated by marine organisms and is the main contributor to radioactive dose to the population. Finally, we identify topics for future research, mainly related to the application of nuclear techniques to the study of oceanographic processes.
Cesium: Global Ocean Distribution
Authors: Inomata Yayoi
Published: December 2011

Since the 1950s Cesium‐137(137Cs) concentrations in the surface waters of the global ocean have been extensively measured in numerous studies. This article, based on the analysis of the137Cs concentrations in the HAM‐global database, summarizes the results of spatial and temporal variations in137Cs concentrations in the surface waters (0–10 m) of the global ocean for the period 1957 to 2005.137Cs in the surface waters of the North Pacific Ocean and North Atlantic Ocean has mainly originated from the nuclear weapon testing global fallout in the late 1950s and early 1960s. In the 1970s and 1980s, the discharge from the nuclear fuel reprocessing plants was the dominant source for the North Atlantic Ocean and its northeast marginal seas. The seas that were largely affected by the fallout of the Chernobyl accident in 1986 were the Baltic, the Black, and the Mediterranean Seas. In the 1990s and 2000s, the137Cs concentrations were decreasing in the global ocean. During this time, the difference in concentrations in the various seas reduced when compared with those in the 1960s and 1970s. In 2005, the most anthropogenic137Cs contaminated area of the global ocean was Baltic Sea, whereas the most undisturbed area was the Antarctic Ocean.137Cs in the surface water had an almost homogeneous distribution in the North Pacific, the equatorial region in the Pacific, and the Indian Ocean. The fact that the apparent‐half residence time (the decreasing rate of137Cs concentration) is almost equal in these regions suggests that the137Cs injected into the western North Pacific Ocean by global fallout was transported to the subtropics and tropics through oceanographic processes. Part of137Cs was recirculated in the Pacific Ocean, and the rest was transported into the Indian Ocean via the Indonesian through flow.
Hydrogen Production from Renewables
Authors: Navarro Rufino M. , Sanchez‐Sanchez M. Cruz , Alvarez‐Galvan M. Consuelo , Fierro Jose Luis G. , Al‐Zaharani Saeed M.
Published: December 2011

Hydrogen is considered to be critical for energy and environmental sustainability. However, as hydrogen is currently produced from fossil fuels, it emits large amounts of carbon dioxide along the reforming steps. The technical challenges to achieve a stable hydrogen economy include improving process efficiencies, lowering the cost of production, and harnessing renewable sources for hydrogen production. Lignocellulosic biomass is one of the most abundant forms of renewable resources. When this precursor is used, virtually no net greenhouse gas emissions result because a natural cycle is maintained, in which carbon is extracted from the atmosphere during plant growth and is released during hydrogen production. This article focuses on recent developments in biomass and biomass‐derived product conversion to H2. The second option explored here is the conversion of solar energy into hydrogen via water‐splitting processes assisted by two‐step metal‐oxide thermochemical cycles or by photosemiconductor catalysts. The conversion of solar energy into a clean fuel (H2) is the most promising technology for the future because large quantities of hydrogen can potentially be generated in a clean and sustainable manner. Undoubtedly, the conversion of solar energy into H2is one of the greatest challenges scientists are facing in the twenty first century. A survey is presented of the advances made in the development of metal oxide redox pairs since the pioneering work by Nakamura in 1977 and in the development of photocatalysts for water splitting under visible light since the first work of Fujishima and Honda in 1972. The very high thermal reduction temperature used for the metal oxide redox pairs developed until now leads to severe sintering, melting, and vaporization of materials, decreasing the efficiency and durability in the cyclic operation. Consequently, the application of material science and engineering to the development of materials with lower reduction temperature and high water‐splitting ability is still a challenge in this scientific area and an overview of the progress is provided in this article. On the other hand, there are still major challenges in the development of photocatalysts with improved efficiencies for hydrogen production from water using solar energy. An overview is provided in this article of research strategies and approaches adopted in the search for photocatalysts for water splitting under visible light (new photocatalyst materials and the control of the synthesis of materials for customizing the crystallinity, electronic structure, and morphology of catalysts at nanometric scale).
Fuel Cells: Intermediate Temperature Solid Oxides
Authors: Atkinson Alan , Kilner John , Skinner Stephen , Brandon Nigel P. , Brett Dan J. L.
Published: December 2011

Fuel cells are electrochemical energy conversion devices that convert chemical energy in fuels directly into electrical energy, without the process of combustion. As a result, they are not constrained by the same thermodynamic limitations as those of heat engines and therefore have the potential to achieve higher efficiencies. High‐temperature solid oxide fuel cells (HT‐SOFCs) operate up to 1000 °C. These fuel cells achieve very high system efficiencies when integrated with gas turbines for large‐scale stationary applications. However, operation at such high temperatures means that the components of the stack need to be predominantly ceramic, in addition to expensive high‐temperature metal alloys. For smaller scale applications, there is a trend to move to lower operating temperatures, into the so‐called intermediate‐temperature (IT) range of 500–750 °C. In doing so, a wider range of construction materials can be used, offering reduced system cost and, in principle, improved performance durability. In this article, we introduce the IT‐SOFC and explain their main operational advantages. We also focus on the combination of inorganic materials and processing routes that go to make reduced temperature SOFC operation possible.
Water Splitting: Thermochemical
Authors: T‐Raissi Ali
Published: December 2011

Hydrogen 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

Nuclease 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

Nuclear 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

LIM 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

Neprilysin (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

Serralysins (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

The 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

Metallocarboxypeptidases (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

Leucine 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

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

Small 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

Calpains 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

The 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

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

The 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

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

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

The 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

Specific 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.
Mitochondrial cytochromec
Authors: Banci Lucia , Assfalg Michael
Published: December 2011

Functional Class

Occurrence

Biological Function

Amino Acid Sequence Information

Protein Production, Purification and Molecular Characterization

Metal Content and Cofactors

Spectroscopy

Structural Studies

Functional Aspects

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Cytochromec2
Authors: Miki Kunio , Sogabe Satoshi
Published: December 2011

Cytochromec2participates 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

Functional Class

Biological Function

Amino Acid Sequence Information

Protein Production, Purification and Molecular Characterization

Metal Content and Cofactors

Spectroscopy

3DStructure

Functional Aspects

Site‐Directed Mutants

Related Articles
Cytochromec553
Authors: Nakagawa Atsushi
Published: December 2011

Cytochromec553in sulfate‐reducing bacteria,Desulfovibrio vulgaris, receives electrons from formate dehydrogenase and lactate dehydrogenase, and then transfers them to cytochromec3. Cytochromec553is a monohemec‐type cytochrome with an absorption band at 553 nm in the reduced form and is the smallestc‐type cytochrome with a molecular weight of 9000. Its three‐dimensional structure has been determined by both x‐ray crystallography and NMR.
Cytochromec6
Authors: Reuter Wolfgang , Wiegand Georg
Published: December 2011

Cytochromec6, or its functional analog copper protein plastocyanin, mediates the intrathylakoidal photosynthetic electron transfer from the always dimeric cytochromeb6fcomplex to the monomeric and/or trimeric Photosystem I (PS I) complex. The high‐potential monoheme protein belongs to the omnipresent cytochromecfamily 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 cytochromec6from various organisms, the real molecular events that occur during its reduction by cytochromeb6fand its oxidation by the reaction center of PS I are presently uncertain. In addition, the specific role of cytochromec6within the hydrogen metabolism in an anaerobic environment is in the focus of interest. However, the presentation of established information about cytochromec6is 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: December 2011

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.
Photosynthetic Reaction Centers of Purple Bacteria
Authors: Lancaster C Roy D , Michel Hartmut
Published: December 2011

Functional Class

Occurrence

Biological Function

Amino Acid Sequence Information

Protein Production, Purification, and Molecular Characterization

Metal Content and Cofactors

Spectroscopy

X‐Ray Structures ofRCsfrom Purple Bacteria

Functional Aspects

Functional Derivatives

Inter‐ and Intramolecular Electron and Proton Transfer and Catalytic Mechanism

Relevance to PhotosystemII

Related Articles
Cytochromec554
Authors: Iverson Tina M , Hendrich Michael P , Arciero David M , Hooper Alan B , Rees Douglas C
Published: December 2011

Cytochrome c554(cyt c554) is a tetra‐hemec‐type cytochrome that participates in the nitrification pathway ofNitrosomonas europaea. In this process, cyt c554functions as the electron acceptor from the enzyme hydroxylamine oxidoreductase that catalyzes the oxidation of hydroxylamine to nitrite. Cyt c554is a predominantly α‐helical protein with four covalently attached hemes. The four hemes are arranged in two pairs, such that the planes of the porphyrin rings are nearly parallel and overlapping at the edges. This type of heme‐stacking has been observed in two other nitrogen cycle proteins: hydroxylamine oxidoreductase and cytochrome c nitrite reductase, an enzyme that catalyzes the reduction of nitrite to ammonia. The relatively unusual spectral properties of cyt c554may reflect interactions between these pairs of stacked hemes.
Nine‐Heme Cytochrome

c
Authors: Arménia Carrondo Maria , Soares Cláudio M , Matias Pedro M
Published: December 2011

Nine heme cytochrome c (9Hcc) is a monomeric multi‐heme cytochrome c found in the sulfate‐reducing bacteria of

Desulfovibrio desulfuricans

(Dd) ATCC 27774 and

Desulfovibrio desulfuricans

Essex 6. The polypeptide chain comprises 296 residues and wraps around nine hemes of type‐c that bind the polypeptide chain through thioether bridges to cysteine residues. This represents the first known structure of a multi‐heme cytochrome where copies of a tetra‐heme cytochrome
c
3
‐like fold are present in the same polypeptide chain.

The high homology between 9Hcc and the C‐terminal region of

Desulfovibrio vulgaris

Hildenborough (DvH) Hmc, as well as the presence of the
9Hcc
gene within an operon similar to that of the DvH Hmc, strongly support the proposal that 9Hcc is the high‐molecular‐weight cytochrome of Dd. Several
in vitro
studies, as well as our crystallographic and modeling studies suggest that cytochrome
c
3
is the mediator between the [NiFe] hydrogenase and 9Hcc in Dd.
Cytochromef/Plastocyanin Complex
Authors: Ubbink M
Published: December 2011

In 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.
Horseradish Peroxidase
Authors: Gajhede Michael
Published: December 2011

Functional Class

Occurrence

Biological Function

Amino Acid Sequence Information

Protein Production, Purification and Molecular Characterization

Metal Content and Cofactors

Spectroscopy

X‐ray Structure of NativeHRPC

Functional Aspects

Functional Derivatives

X‐ray Structure ofHRPC:Benzhydroxamic Acid Complex

X‐ray Structure ofHRPC:Ferulic Acid Complex

X‐ray Structure of TernaryHRPC:FA:CN−Complex

Catalytic Mechanism

Acknowledgements

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Myeloperoxidase
Authors: Fenna Roger E
Published: December 2011

Functional Class

Occurrence

Biological Function

Amino Acid Sequence Information

Protein Production, Purification and Molecular Characterization

Metal Content and Cofactors

Activity Test

Spectroscopy

X‐Ray Crystal Structure ofMPO

Functional Aspects

Functional Derivatives

Catalytic Mechanism

Related Articles
Arthromyces Peroxidase
Authors: Fukuyama Keiichi
Published: December 2011

Heme peroxidase catalyzes the oxidation of a variety of compounds by utilizing hydrogen peroxide. The resting peroxidase reacts with hydrogen peroxide to yield an intermediate compound I, which is reduced to the resting stateviathe second intermediate compound II, by the use of reducing substrates. The reducing substrates include naturally occurring organic compounds such as phenols and ascorbic acid, diagnostic reagents such as luminol and 4‐amino‐antipyrine, as well as inorganic compounds such as halide ions, ferrocyanide, and isothiocyanate.Arthromycesperoxidase is a class II peroxidase in the plant peroxidase superfamily, and has the characteristics of giving extraordinarily high chemiluminescence in the oxidation of luminol.
Chloroperoxidase
Authors: Sundaramoorthy Munirathinam
Published: December 2011

Chloroperoxidase (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.
Prostaglandin EndoperoxideH2Synthases‐1 and ‐2
Authors: Michael Garavito R
Published: December 2011

The prostaglandin endoperoxide H2synthase (PGHS) isozymes 1 and 2 are membrane bound, heme‐dependent enzymes that catalyze the committed step in the conversion of polyunsaturated fatty acids to prostanoids and thromboxanes. The PGHS isozymes, which are also known as cyclooxygenases, produce prostaglandin H2in two sequential enzymatic steps – a bis‐oxygenase (cyclooxygenase) reaction generates prostaglandin G2from arachidonic acid and a hydroperoxidase reaction creates the final product, prostaglandin H2. The PGHS isozymes are also the primary targets of nonsteroidal anti‐inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, and recent pharmacological research efforts have led to the development of isoform selective drugs like Celebrex® and Vioxx®. In this chapter, we discuss the biochemistry, enzymology, and the structural biology of the PGHS isozymes and their relevance to prostanoid physiology and NSAID pharmacology.
CytochromeP450
Authors: Li Huiying
Published: December 2011

Functional Class

Occurrence

Biological Function

Amino Acid Sequence Information

Protein Production, Purification and Molecular Characterization

Metal Content and Cofactors

Activity Test

Spectroscopy

X‐Ray Structure of CytochromesP450

Structures of Functional Intermediate

Structure‐Based Sequence Alignment

Functional Aspects

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