1q7a: Difference between revisions

Revision as of 15:36, 21 February 2008

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

OverviewOverview

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.

About this StructureAbout this Structure

1Q7A is a Single protein structure of sequence from Daboia russellii russellii with , and as ligands. Active as Phospholipase A(2), with EC number 3.1.1.4 Full crystallographic information is available from OCA.

ReferenceReference

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., Singh N, Jabeen T, Somvanshi RK, Sharma S, Dey S, Singh TP, Biochemistry. 2004 Nov 23;43(46):14577-83. PMID:15544328

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-[[Image:1q7a.jpg|left|200px]]<br /><applet load="1q7a" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1q7a.jpg|left|200px]]<br /><applet load="1q7a" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1q7a, resolution 1.6&Aring;" />
 '''Crystal structure of the complex formed between russell's viper phospholipase A2 and an antiinflammatory agent oxyphenbutazone at 1.6A resolution'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-Q7A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Daboia_russellii_russellii Daboia russellii russellii] with SO4, OPB and MOH as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Q7A OCA].
+Q7A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Daboia_russellii_russellii Daboia russellii russellii] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=OPB:'>OPB</scene> and <scene name='pdbligand=MOH:'>MOH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q7A OCA].
 ==Reference==
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 [[Category: Sharma, S.]]
 [[Category: Singh, N.]]
-[[Category: Singh, T.P.]]
+[[Category: Singh, T P.]]
 [[Category: MOH]]
 [[Category: OPB]]
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 [[Category: venom]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 00:26:50 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:36:43 2008''