title: Crystal structure of a Trimeresurus mucrosquamatus venom metalloproteinase providing new insights into the inhibition by endogenous tripeptide inhibitors.
abstract: The crystal structure of TM-1, a P-I class snake-venom metalloproteinase (SVMP) from the Trimeresurus mucrosquamatus venom, was determined at 1.8-Å resolution. The structure exhibits the typical feature of SVMPs and is stabilized by three disulfide linkages. The active site shows a deep S1' substrate-binding pocket limited by the non-conserved Pro174 at the bottom. Further comparisons with other SVMPs suggest that the deep S1' site of TM-1 correlates with its high inhibition sensitivity to the endogenous tripeptide inhibitors. Proteolytic specificity analysis revealed that TM-1 prefers substrates having a moderate-size and hydrophobic residue at the P1' position, consistent with our structural observation.
authors.affiliation: Institute of Biochemical Sciences, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Tsung-Lin
authors.initials: TL
authors.lastname: Chou
authors.forename: Cheng-Heng
authors.initials: CH
authors.lastname: Wu
authors.forename: Kai-Fa
authors.initials: KF
authors.lastname: Huang
authors.forename: Andrew H-J
authors.initials: AH
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D003435:Crotalid Venoms / Q000737:chemistry*; D003460:Crystallization; D057927:Hydrophobic and Hydrophilic Interactions; D045726:Metalloproteases / Q000737:chemistry*; D008969:Molecular Sequence Data; D010879:Piperazines / Q000737:chemistry; D011480:Protease Inhibitors / Q000737:chemistry*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D017819:Viperidae
chemical_list: D003435:Crotalid Venoms; D010879:Piperazines; D011480:Protease Inhibitors; C098227:TM 1; C029748:Trimeresurus venoms; D045726:Metalloproteases
keywords: S1′ substrate-binding pocket; Snake-venom metalloproteinase; Trimeresurus mucrosquamatus; Tripeptide inhibitor