Prediction of EF‐hand calcium‐binding proteins and analysis of bacterial EF‐hand proteins

Zhou, Yubin; Yang, Wei; Kirberger, Michael; Lee, Hsiau‐Wei; Ayalasomayajula, Gayatri; Yang, Jenny J.

doi:10.1002/prot.21139

Cited by 140 publications

(152 citation statements)

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“…The helix-loop-helix EF-hand moiety is one of the most common motifs in proteins of bacteria, archaea, and eukaryotes (28,73), and by binding to Ca 2ϩ this motif may undergo conformational changes enabling Ca 2ϩ -modulated functions, as seen in the trigger or sensor proteins calmodulin and troponin C (27,32), or may control the concentration of Ca 2ϩ to maintain local Ca 2ϩ homeostasis, as reported in buffering proteins such as parvalbumin (29) and calbindin D 9k (56). The coordination of Ca 2ϩ in EF-hand motifs is fulfilled by adopting a pentagonal bipyramidal geometry.…”

mentioning

confidence: 99%

Identification of a Ca ²⁺ -Binding Domain in the Rubella Virus Nonstructural Protease

Zhou¹,

Tzeng

Yang³

et al. 2007

J Virol

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The rubella virus (RUB) nonstructural protein (NS) open reading frame (ORF) encodes a polypeptide ‫؍‬ 4.1°C). The infectivity of an RUB infectious cDNA clone containing the mutations D1210A/D1217A was decreased by ϳ20-fold in comparison to the wild-type (wt) clone, and these mutations rapidly reverted to the wt sequence. The NS protease containing these mutations was less efficient at precursor cleavage than the wt NS protease at 35°C, and the mutant NS protease was temperature sensitive at 39°C, confirming that the Ca 2؉ -binding loop played a structural role in the NS protease and was specifically required for optimal stability under physiological conditions.

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mentioning

confidence: 99%

Identification of a Ca ²⁺ -Binding Domain in the Rubella Virus Nonstructural Protease

Zhou¹,

Tzeng

Yang³

et al. 2007

J Virol

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“…Strand-loop-strand structures in blades A, B, C, F, G, and H, especially aspartic acid residues in the first position of the loop, are well conserved ( Fig. 3A; the structure in blade B is shown in the upper inset) and similar to the EF-hand-like calcium-binding motif (70) in alkaline protease from Pseudomonas aeruginosa (71) and integrin ␣ V ␤ 3 from Homo sapiens (72). Blade E contains two calcium ions surrounded by two loops.…”

Section: Resultsmentioning

confidence: 95%

A Novel Structural Fold in Polysaccharide Lyases

Ochiai

Itoh

Maruyama

et al. 2007

Journal of Biological Chemistry

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Rhamnogalacturonan (RG) lyase produced by plant pathogenic and saprophytic microbes plays an important role in degrading plant cell walls. An extracellular RG lyase YesW from saprophytic Bacillus subtilis is a member of polysaccharide lyase family 11 and cleaves glycoside bonds in polygalacturonan as well as RG type-I through a ␤-elimination reaction. Crystal structures of YesW and its complex with galacturonan disaccharide, a reaction product analogue, were determined at 1.4 and 2.5 Å resolutions with final R-factors of 16.4% and 16.6%, respectively. The enzyme is composed of an eight-bladed ␤-propeller with a deep cleft in the center as a basic scaffold, and its structural fold has not been seen in polysaccharide lyases analyzed thus far. Structural analysis of the disaccharide-bound YesW and a site-directed mutagenesis study suggested that Arg-452 and Lys-535 stabilize the carboxyl group of the acidic polysaccharide molecule and Tyr-595 makes a stack interaction with the sugar pyranose ring. In addition to amino acid residues binding to the disaccharide, one calcium ion, which is coordinated by Asp-401, Glu-422, His-363, and His-399, may mediate the enzyme activity. This is, to our knowledge, the first report of a new structural category with a ␤-propeller fold in polysaccharide lyases and provides structural insights into substrate binding by RG lyase.Plant cell wall degradation is essential for plant pathogenic and saprophytic microbes to invade plants. The plant cell wall mainly consists of polysaccharides and proteins, with polysaccharides being more abundant. These polysaccharides are divided into three groups, cellulose, hemicellulose, and pectin (1). Pectin is more soluble in water than cellulose and hemicellulose, suggesting that this polysaccharide is the preferred target for plant-associated microbes. Pectin is further divided to three regions, i.e. polygalacturonan, rhamnogalacturonan type-I (RG-I), 2 and rhamnogalacturonan type-II (RG-II). In pectin molecules, polygalacturonan is present as a linear backbone, and RG-I and RG-II are attached to the backbone as branched chains (2-4). RG-I is a polymer with a disacchariderepeating unit consisting of L-rhamnopyranose and D-galactopyranouronic acid (GalA) as a main chain, and arabinans and galactans are attached to the main chain (5). RG-II has a backbone of polygalacturonan, and its side chains consist of a complex of ϳ30 monosaccharides, including rare sugars such as apiose and aceric acid (6). These plant cell wall polysaccharides become substrates to be degraded through reactions of polysaccharide hydrolases and/or lyases produced by plant pathogenic and saprophytic microbes. Hydrolases cleave glycoside bonds in polysaccharides via hydrolysis, and lyases do so by ␤-elimination reactions (7,8).The degradation pathway for the polygalacturonan region has been characterized extensively in microbes (9 -12). The structure and function relationships of polygalacturonan-degrading enzymes, including hydrolases and lyases have also been well documented (13)(...

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“…It is also interesting that the above TERM appears to correspond to the most structurally conserved portion of the EF hand and excludes the binding loop and much of the N-terminal helix (Fig. 5 A-C), both of which are known to exhibit substantial variation (63). Additional examples of functionally linked TERMs, including a modular metalcoordinating motif and water-binding TERMs, are presented in SI Appendix, SI Results and Figs.…”

Section: A Small Number Of Terms Describe Most Of the Structural Univmentioning

confidence: 96%

Tertiary alphabet for the observable protein structural universe

Mackenzie

Zhou

Grigoryan

2016

Proc. Natl. Acad. Sci. U.S.A.

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Here, we systematically decompose the known protein structural universe into its basic elements, which we dub tertiary structural motifs (TERMs). A TERM is a compact backbone fragment that captures the secondary, tertiary, and quaternary environments around a given residue, comprising one or more disjoint segments (three on average). We seek the set of universal TERMs that capture all structure in the Protein Data Bank (PDB), finding remarkable degeneracy. Only ∼600 TERMs are sufficient to describe 50% of the PDB at sub-Angstrom resolution. However, more rare geometries also exist, and the overall structural coverage grows logarithmically with the number of TERMs. We go on to show that universal TERMs provide an effective mapping between sequence and structure. We demonstrate that TERM-based statistics alone are sufficient to recapitulate close-to-native sequences given either NMR or X-ray backbones. Furthermore, sequence variability predicted from TERM data agrees closely with evolutionary variation. Finally, locations of TERMs in protein chains can be predicted from sequence alone based on sequence signatures emergent from TERM instances in the PDB. For multisegment motifs, this method identifies spatially adjacent fragments that are not contiguous in sequence-a major bottleneck in structure prediction. Although all TERMs recur in diverse proteins, some appear specialized for certain functions, such as interface formation, metal coordination, or even water binding. Structural biology has benefited greatly from previously observed degeneracies in structure. The decomposition of the known structural universe into a finite set of compact TERMs offers exciting opportunities toward better understanding, design, and prediction of protein structure.tertiary motif | structural degeneracy | protein structural universe | sequence-structure relationships | structural modularity I n this work, we aim to decompose the protein structure space into its basic elements as a way of understanding its design principles and describing its limits. Reductionist representations of protein structure have been of long-standing interest (1), with many studies having shown degeneracy at various structural levels (2-5). Features ranging from backbone or side-chain dihedral angles (6, 7) to domains and folds (8, 9) have been classified, and structural basins of attraction have been found in select motifs (10-17), offering a glimpse of a modular space with frequently repeating elements. The reason behind this modularity appears to be a combination of evolutionary history and the fundamental physics of structure. In particular, degeneracy at the level of domains, folds, and functional modules is likely strongly influenced by evolution, whereby such elements recur in different proteins often because of a common ancestor (18,19). On the other hand, statistics of more detailed structural features are better explained from the thermodynamic perspective. For example, observed Ramachandran backbone dihedral angle preferences are largely determined...

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Prediction of EF‐hand calcium‐binding proteins and analysis of bacterial EF‐hand proteins

Cited by 140 publications

References 90 publications

Identification of a Ca ²⁺ -Binding Domain in the Rubella Virus Nonstructural Protease

Identification of a Ca ²⁺ -Binding Domain in the Rubella Virus Nonstructural Protease

A Novel Structural Fold in Polysaccharide Lyases

Tertiary alphabet for the observable protein structural universe

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Prediction of EF‐hand calcium‐binding proteins and analysis of bacterial EF‐hand proteins

Cited by 140 publications

References 90 publications

Identification of a Ca 2+ -Binding Domain in the Rubella Virus Nonstructural Protease

Identification of a Ca 2+ -Binding Domain in the Rubella Virus Nonstructural Protease

A Novel Structural Fold in Polysaccharide Lyases

Tertiary alphabet for the observable protein structural universe

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Identification of a Ca ²⁺ -Binding Domain in the Rubella Virus Nonstructural Protease

Identification of a Ca ²⁺ -Binding Domain in the Rubella Virus Nonstructural Protease