Crystal structure of RVV-X: an example of evolutionary gain of specificity by ADAM proteinases.
Russell's viper venom factor X activator (RVV-X) is a heterotrimeric metalloproteinase with a mammalian ADAM-like heavy chain and two lectin-like light chains. The crystal structure of RVV-X has been determined at 2.9 A resolution and shows a hook-spanner-wrench-like architecture, in which the metalloproteinase/disintegrin region constitutes a hook, and the lectin-like domains constitute a handle. A 6.5nm separation between the catalytic site and a putative exosite suggests a docking model for factor X. The structure provides a typical example of the molecular evolution of multi-subunit proteins and insights into the molecular basis of target recognition and proteolysis by ADAM/adamalysin/reprolysin proteinases.
Department of Cardiac Physiology, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. stakeda@ri.ncvc.go.jp
Soichi
S
Takeda
Tomoko
T
Igarashi
Hidezo
H
Mori
D051722:ADAM Proteins / Q000737:chemistry*; D022801:Complementarity Determining Regions / Q000737:chemistry; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D008666:Metalloendopeptidases / Q000737:chemistry*; D045726:Metalloproteases / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry; D013379:Substrate Specificity; D014757:Viper Venoms / Q000737:chemistry*
D022801:Complementarity Determining Regions; D021122:Protein Subunits; D014757:Viper Venoms; D045726:Metalloproteases; D051722:ADAM Proteins; D008666:Metalloendopeptidases; C476775:factor X activator, Russell's viper