PDBsum entry: 1cl5

Hydrolase

PDB id: 1cl5

Contents

Protein chains

121 a.a. *

Waters ×160

* Residue conservation analysis

PDB id:

1cl5

Name:

Hydrolase

Title:

Crystal structure of phospholipase a2 from daboia russelli pulchella

Structure:

Protein (phospholipase a2). Chain: a, b. Ec: 3.1.1.4

Source:

Daboia russellii pulchella. Organism_taxid: 97228. Strain: pulchella. Secretion: venom

Biol. unit:

Dimer (from PQS)

Resolution:

2.45Å R-factor: 0.188 R-free: 0.267

Authors:

V.Chandra,P.Kaur,T.P.Singh

Key ref:

V.Chandra et al. (2000). Three-dimensional structure of a presynaptic neurotoxic phospholipase A2 from Daboia russelli pulchella at 2.4 A resolution. J Mol Biol, 296, 1117-1126. PubMed id: 10686108 DOI: 10.1006/jmbi.2000.3537

Date:

06-May-99 Release date: 12-May-99

Protein chains

P59071  (PA28_DABRR) -  Phospholipase A2 VRV-PL-VIIIa

Seq: 121 a.a.

Struc: 121 a.a.

Enzyme reactions

• Enzyme class: E.C.3.1.1.4 - Phospholipase A(2).
• Reaction: Phosphatidylcholine + H₂O = 1-acylglycerophosphocholine + a carboxylate
• Cofactor: Calcium

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (2 terms)
• Biological process: lipid catabolic process (4 terms)
• Biochemical function: hydrolase activity (4 terms)

reference

DOI no: 10.1006/jmbi.2000.3537

J Mol Biol 296:1117-1126 (2000)

PubMed id: 10686108

Three-dimensional structure of a presynaptic neurotoxic phospholipase A2 from Daboia russelli pulchella at 2.4 A resolution.

V.Chandra, P.Kaur, A.Srinivasan, T.P.Singh.

ABSTRACT

The phospholipase A(2 )from Daboia russelli pulchella (DPLA(2)) is the only known member of subclass II of group IIA. The three-dimensional structure of this presynaptic neurotoxic DPLA(2) enzyme has been determined at 2.4 A resolution. The structure was determined by the molecular replacement method using the model Crotalus atrox, and refined using X-PLOR to a final R-factor of 18.8 % for all data in the resolution range 20.0 A-2.4 A. The final refined model comprises 1888 atoms from two crystallographically independent protein molecules and 160 water oxygen atoms. The overall folding of DPLA(2), with three long helices and two short antiparallel beta-strands is grossly similar to those observed for other PLA(2)s. In the present structure, the calcium binding site is empty but the conformation of the calcium binding loop is similar to those observed in the calcium bound states. Two spatially adjacent regions of residues 55-61 (a typical beta-turn I) and 83-94 (a well defined loop) are remarkably different in conformation, electrostatic characteristics and inter-segmental interactions from those found in non-neurotoxic PLA(2)s. Yet another striking structural feature in DPLA(2 )pertains to the stretch of residues 53-77, which has a series of positively charged residues protruding outwardly. The above segment is presumed to be involved in the anticoagulant activity. A unique hydrophobic patch including residues Leu17, Ala18, Ile19, Pro20, Phe106 and Leu110 is found on the surface together with an equally emphatic region of -OH groups containing residues such as Ser21, Tyr22, Ser23, Ser24, Tyr25 and Tyr28. The interactions between two molecules of DPLA(2) in the asymmetric unit are remarkably different from those observed in the standard dimers and trimers of PLA(2)s, leaving the enzyme's active site fully exposed for enzyme-substrate reactions, it makes this structure one of the most favourable examples for structure-based drug design through soaking experiments.

Selected figure(s)

Figure 3.
Figure 3. (a) Superimposition of C^α traces of DPLA[2] (thick lines) and VPLA[2] (thin lines). The r.m.s. difference for the C^α atoms is 1.2 Å. The corresponding shifts for the neurotoxic (55–61 and 85–94), and anticoagulant (53–77) fragments are 1.8 Å and 1.3 Å, respectively. (b) Protruding side-chains of basic residues for the anticoagulant site.

Figure 4.
Figure 4. (a) The association of molecules A and B showing a number of residues from both the molecules (black) and solvent molecules (red) involved in the interactions between two molecules: molecule A, Leu2, Leu17, Ala18, Ile19, Pro20, Trp31, Arg43, Phe46, Ser70, Arg72, Met118, Leu119 and Asp122; molecule B, Thr36, Ala40, Arg43, Phe46, Val47, Asn54, Glu97, Lys100, Ile104, Gln108, Asn111, Leu130, Lys131 and Cys133 and 31 solvent molecules. (b) Spatially two adjacent fragments 55–61 and 85–94. The segment 55–61 forms a β-turn I with a hydrogen bond between Leu55 (O) and Cys61 (N). A tight loop, 85-94, is stabilized by a number of intra-loop hydrogen bonds which are indicated by dotted lines. The inter-segmental hydrogen bonds (red, broken lines) are also indicated.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 296, 1117-1126) copyright 2000.

Figures were selected by an automated process.