The 1.35 Å structure of cadmium-substituted TM-3, a snake-venom metalloproteinase from Taiwan habu: Elucidation of a TNFα-converting enzyme-like active-site structure with a distorted octahedral geometry of cadmium

Kai Fa Huang, Shyh Horng Chiou, Tzu Ping Ko, Jeu Ming Yuann, Andrew H.J. Wang

研究成果: 雜誌貢獻文章同行評審

29 引文 斯高帕斯(Scopus)

摘要

The crystal structure of TM-3, a small snake-venom metalloproteinase (SVMP) isolated from Taiwan habu (Trimeresurus mucrosquamatus), was determined at 1.35 Å resolution with resultant R and Rfree values of 0.181 and 0.204, respectively. The overall structure of TM-3 is an oblate ellipsoid that contains three disulfide crosslinks, Cys118-Cys197, Cys159-Cys181 and Cys161-Cys164. It exhibits the typical structural features of SVMPs and is closely related to the structure of the catalytic proteinase domain of TNFα-converting enzyme (TACE). In the present structure, the essential catalytic zinc ion was found to be replaced by a cadmium ion during crystallization, as revealed by atomic absorption analysis and X-ray data. This cadmium ion is bound to six ligands, including three conserved histidines and three water molecules, displaying the coordination geometry of a distorted octahedron. One of the water molecules is proposed to play the role of stabilizing the tetrahedral intermediate during the catalysis of SVMPs. The putative S′1 specificity pocket of TM-3 is relatively shallow, in contrast to the deep pockets of adamalysin II, atrolysin C and H2-proteinase, but is similar to those in acutolysin A and TACE. The shallow pocket is a consequence of the presence of the non-conserved disulfide bond Cys159-Cys181 and the residue Gln174 at the bottom of the S′1 pocket. The results indicate that the active-site structure of TM-3, among the know structures of SVMPs examined thus far, is most similar to that of TACE owing to their close disulfide configurations and the S′1 specificity pocket.

原文英語
頁(從 - 到)1118-1128
頁數11
期刊Acta Crystallographica Section D: Biological Crystallography
58
發行號7
DOIs
出版狀態已發佈 - 2002
對外發佈

ASJC Scopus subject areas

  • 結構生物學

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