Sequence and crystal structure determination of a basic phospholipase A2 from common krait ( Bungarus caeruleus ) at 2.4 Å resolution: identification and characterization of its pharmacological sites 1 1Edited by R. Huber

Singh, Garima; Gourinath, S.; Sharma, Sujata; Paramasivam, M.; Srinivasan, Alagiri; Singh, T.P.

doi:10.1006/jmbi.2001.4550

Cited by 53 publications

(33 citation statements)

References 35 publications

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“…Yet, a significant degree of homology is observed between tertiary structures of various PLA2s, which typically are made of three helices, two short helices, a b-wing and six to seven loops. 90 The catalytic site has been reported to comprise of one Asp, one His and two Tyr residues. 93 We observed an Asp/His/ Met/Gln/Tyr/Tyr pattern recurring in 19 of the 20 proteins of this superfamily with matching residue positions with the reported active site.…”

Section: Recurring Structural Patterns In Protein Familiesmentioning

confidence: 99%

Functional Sites in Protein Families Uncovered via an Objective and Automated Graph Theoretic Approach

Wangikar

Tendulkar

Ramya

et al. 2003

Journal of Molecular Biology

105

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We report a method for detection of recurring side-chain patterns (DRESPAT) using an unbiased and automated graph theoretic approach. We first list all structural patterns as sub-graphs where the protein is represented as a graph. The patterns from proteins are compared pairwise to detect patterns common to a protein pair based on content and geometry criteria. The recurring pattern is then detected using an automated search algorithm from the all-against-all pair-wise comparison data of proteins. Intra-protein pattern comparison data are used to enable detection of patterns recurring within a protein. A method has been proposed for empirical calculation of statistical significance of recurring pattern. The method was tested on 17 protein sets of varying size, composed of non-redundant representatives from SCOP superfamilies. Recurring patterns in serine proteases, cysteine proteases, lipases, cupredoxin, ferredoxin, ferritin, cytochrome c, aspartoyl proteases, peroxidases, phospholipase A2, endonuclease, SH3 domain, EF-hand and lectins show additional residues conserved in the vicinity of the known functional sites. On the basis of the recurring patterns in ferritin, EF-hand and lectins, we could separate proteins or domains that are structurally similar yet different in metal ion-binding characteristics. In addition, novel recurring patterns were observed in glutathione-S-transferase, phospholipase A2 and ferredoxin with potential structural/functional roles. The results are discussed in relation to the known functional sites in each family. Between 2000 and 50,000 patterns were enumerated from each protein with between ten and 500 patterns detected as common to an evolutionarily related protein pair. Our results show that unbiased extraction of functional site pattern is not feasible from an evolutionarily related protein pair but is feasible from protein sets comprising five or more proteins. The DRESPAT method does not require a user-defined pattern, size or location of the pattern and therefore, has the potential to uncover new functional sites in protein families.

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Section: Recurring Structural Patterns In Protein Familiesmentioning

confidence: 99%

Functional Sites in Protein Families Uncovered via an Objective and Automated Graph Theoretic Approach

Wangikar

Tendulkar

Ramya

et al. 2003

Journal of Molecular Biology

105

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“…On the other hand the catalytic residues and the substratebinding site are well characterized in PLA 2 enzymes. Threedimensional structures of various isoforms of PLA 2 from a number of sources have been determined (Thunnissen et al, 1990;Scott et al, 1990;Scott et al, 1991;Chandra et al, 2001;Singh et al, 2001;Banumathi et al, 2001;Gu et al, 2002;Matoba et al, 2002;Xu et al, 2003aXu et al, , 2003bJasti et al, 2004;Lok et al, 2005). There have also been extensive investigations to understand their (www.interscience.wiley.com) DOI:10.1002/jmr.960 catalytic actions and various ligands have also been designed to inhibit their enzymatic function.…”

mentioning

confidence: 99%

Simultaneous inhibition of anti‐coagulation and inflammation: crystal structure of phospholipase A₂ complexed with indomethacin at 1.4 Å resolution reveals the presence of the new common ligand‐binding site

Singh

Kumar

et al. 2009

J of Molecular Recognition

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A novel ligand-binding site with functional implications has been identified in phospholipase A(2) (PLA(2)). The binding of non-steroidal anti-inflammatory agent indomethacin at this site blocks both catalytic and anti-coagulant actions of PLA(2). A group IIA PLA(2) has been isolated from Daboia russelli pulchella (Russell's viper) which is enzymatically active as well as induces a strong anti-coagulant action. The binding studies have shown that indomethacin reduces the effects of both anti-coagulant and pro-inflammatory actions of PLA(2). A group IIA PLA(2) was co-crystallized with indomethacin and the structure of the complex has been determined at 1.4 A resolution. The structure determination has revealed the presence of an indomethacin molecule in the structure of PLA(2) at a site which is distinct from the conventional substrate-binding site. One of the carboxylic group oxygen atoms of indomethacin interacts with Asp 49 and His 48 through the catalytically important water molecule OW 18 while the second carboxylic oxygen atom forms an ionic interaction with the side chain of Lys 69. It is well known that the residues, His 48 and Asp 49 are essential for catalysis while Lys 69 is a part of the anti-coagulant loop (residues, 54-77). Indomethacin binds in such a manner that it blocks the access to both, it works as a dual inhibitor for catalytic and anti-coagulant actions of PLA(2). This new binding site in PLA(2) has been observed for the first time and indomethacin is the first compound that has been shown to bind at this novel site resulting in the prevention of anti-coagulation and inflammation.

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“…Consider, for example, the unit cells of phospholipase A 2 discussed by Le Trong & Stenkamp (2007). They present three alternative cells from three different PDB entries that are actually for the same structure: (57.98, 57.98, 57.98, 92.02, 92.02, 92.02) from entry 1fe5 (Singh et al, 2001) in space group R32, (80.36, 80.36, 99.44, 90, 90, 120) from entry 1u4j (Singh et al, 2005b) and (80.949, 80.572, 57.098, 90.0, 90.35, 90.0) from entry 1g2x (Singh et al, 2005a) in space group C2. No simple range search can bring these three cells together.…”

Section: Comparison Of Search Methodsmentioning

confidence: 99%

The geometry of Niggli reduction:SAUC– search of alternative unit cells

et al. 2014

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A database of lattices using the G 6 representation of the Niggli-reduced cell as the search key provides a more robust and complete search than older techniques. Searching is implemented by finding the distance from the probe cell to other cells using a topological embedding of the Niggli reduction in G 6 , so that all cells representing similar lattices will be found. The embedding provides the first fully linear measure of distances between unit cells. Comparison of results with those from older cell-based search algorithms suggests significant value in the new approach.

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Sequence and crystal structure determination of a basic phospholipase A2 from common krait ( Bungarus caeruleus ) at 2.4 Å resolution: identification and characterization of its pharmacological sites 1 1Edited by R. Huber

Cited by 53 publications

References 35 publications

Functional Sites in Protein Families Uncovered via an Objective and Automated Graph Theoretic Approach

Functional Sites in Protein Families Uncovered via an Objective and Automated Graph Theoretic Approach

Simultaneous inhibition of anti‐coagulation and inflammation: crystal structure of phospholipase A₂ complexed with indomethacin at 1.4 Å resolution reveals the presence of the new common ligand‐binding site

The geometry of Niggli reduction:SAUC– search of alternative unit cells

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Sequence and crystal structure determination of a basic phospholipase A2 from common krait ( Bungarus caeruleus ) at 2.4 Å resolution: identification and characterization of its pharmacological sites 1 1Edited by R. Huber

Cited by 53 publications

References 35 publications

Functional Sites in Protein Families Uncovered via an Objective and Automated Graph Theoretic Approach

Functional Sites in Protein Families Uncovered via an Objective and Automated Graph Theoretic Approach

Simultaneous inhibition of anti‐coagulation and inflammation: crystal structure of phospholipase A2 complexed with indomethacin at 1.4 Å resolution reveals the presence of the new common ligand‐binding site

The geometry of Niggli reduction:SAUC– search of alternative unit cells

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Simultaneous inhibition of anti‐coagulation and inflammation: crystal structure of phospholipase A₂ complexed with indomethacin at 1.4 Å resolution reveals the presence of the new common ligand‐binding site