CRYSTAL-STRUCTURE OF PHOSPHOLIPASE-A(2) FROM INDIAN COBRA REVEALS A TRIMERIC ASSOCIATION

被引:72
作者
FREMONT, DH [1 ]
ANDERSON, DH [1 ]
WILSON, IA [1 ]
DENNIS, EA [1 ]
XUONG, NH [1 ]
机构
[1] SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA
关键词
X-RAY CRYSTALLOGRAPHY; PROTEIN STRUCTURE; PROTEIN TRIMER; MOLECULAR REPLACEMENT;
D O I
10.1073/pnas.90.1.342
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Phospholipase A2 (PLA2) from Indian cobra venom (Naja naja naja) was crystallized from ethanol in space group P4(3)2(1)2 in the presence of Ca2+. The x-ray crystal structure was determined to 2.3-angstrom resolution by molecular replacement techniques using a theoretical model constructed from homologous segments of the bovine pancreatic, porcine pancreatic, and rattlesnake venom crystal structures. The structure was refined to an R value of 0.174 for 17,542 reflections between 6.0- and 2.3-angstrom resolution (F > 2sigma), including 148 water molecules. The 119-amino acid enzyme has an overall architecture strikingly similar to the other known PLA2 structures with regions implicated in catalysis showing the greatest structural conservation. Unexpectedly, three monomers were found to occupy the asymmetric unit and are oriented with their catalytic sites facing the pseudo-threefold axis with almost-equal-to 15% of the solvent accessible surface of each monomer buried in trimer contacts. The majority of the interactions at the subunit interfaces are made by residues unique to PLA2 sequences from cobra and krait venoms. The possible relevance of this unique trimeric structure is considered.
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页码:342 / 346
页数:5
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