1Q7A

Crystal structure of the complex formed between russell's viper phospholipase A2 and an antiinflammatory agent oxyphenbutazone at 1.6A resolution

Summary for 1Q7A

• Entry DOI: 10.2210/pdb1q7a/pdb
• Related: 1CL5 1OYF
• Descriptor: Phospholipase A2 VRV-PL-VIIIa, SULFATE ION, 4-BUTYL-1-(4-HYDROXYPHENYL)-2-PHENYLPYRAZOLIDINE-3,5-DIONE, ... (5 entities in total)
• Functional Keywords: phospholipase a2, venom, antiinflammatory compound, hydrolase
• Biological source: Daboia russellii pulchella
• Cellular location: Secreted: P59071
• Total number of polymer chains: 1
• Total formula weight: 14178.31

Authors

Singh, N.,Jabeen, T.,Sharma, S.,Singh, T.P. (deposition date: 2003-08-17, release date: 2004-05-11, Last modification date: 2024-10-30)

Primary citation

Singh, N.,Jabeen, T.,Somvanshi, R.K.,Sharma, S.,Dey, S.,Singh, T.P.
Phospholipase A2 as a target protein for nonsteroidal anti-inflammatory drugs (NSAIDS): crystal structure of the complex formed between phospholipase A2 and oxyphenbutazone at 1.6 A resolution.
Biochemistry, 43:14577-14583, 2004

PubMed Abstract: Phospholipase A(2) (PLA(2); EC 3.1.1.4) is a key enzyme involved in the production of proinflammatory mediators known as eicosanoids. The binding of the substrate to PLA(2) occurs through a well-formed hydrophobic channel. To determine the viability of PLA(2) as a target molecule for the structure-based drug design against inflammation, arthritis, and rheumatism, the crystal structure of the complex of PLA(2) with a known anti-inflammatory compound oxyphenbutazone (OPB), which has been determined at 1.6 A resolution. The structure has been refined to an R factor of 0.209. The structure contains 1 molecule each of PLA(2) and OPB with 2 sulfate ions and 111 water molecules. The binding studies using surface plasmon resonance show that OPB binds to PLA(2) with a dissociation constant of 6.4 x 10(-8) M. The structure determination has revealed the presence of an OPB molecule at the binding site of PLA(2). It fits well in the binding region, thus displaying a high level of complementarity. The structure also indicates that OPB works as a competitive inhibitor. A large number of hydrophobic interactions between the enzyme and the OPB molecule have been observed. The hydrophobic interactions involving residues Tyr(52) and Lys(69) with OPB are particularly noteworthy. Other residues of the hydrophobic channel such as Leu(3), Phe(5), Met(8), Ile(9), and Ala(18) are also interacting extensively with the inhibitor. The crystal structure clearly reveals that the binding of OPB to PLA(2) is specific in nature and possibly suggests that the basis of its anti-inflammatory effects may be due to its binding to PLA(2) as well.

PubMed: 15544328
DOI: 10.1021/bi0483561

Experimental method

X-RAY DIFFRACTION (1.6 Å)