title: Snake venom metalloproteinases: structure, function and relevance to the mammalian ADAM/ADAMTS family proteins.
abstract: Metalloproteinases are among the most abundant toxins in many Viperidae venoms. Snake venom metalloproteinases (SVMPs) are the primary factors responsible for hemorrhage and may also interfere with the hemostatic system, thus facilitating loss of blood from the vasculature of the prey. SVMPs are phylogenetically most closely related to mammalian ADAM (a disintegrin and metalloproteinase) and ADAMTS (ADAM with thrombospondin type-1 motif) family of proteins and, together with them, constitute the M12B clan of metalloendopeptidases. Large SVMPs, referred to as the P-III class of SVMPs, have a modular architecture with multiple non-catalytic domains. The P-III SVMPs are characterized by higher hemorrhagic and more diverse biological activities than the P-I class of SVMPs, which only have a catalytic domain. Recent crystallographic studies of P-III SVMPs and their mammalian counterparts shed new light on structure-function properties of this class of enzymes. The present review will highlight these structures, particularly the non-catalytic ancillary domains of P-III SVMPs and ADAMs that may target the enzymes to specific substrates. This article is part of a Special Issue entitled: Proteolysis 50years after the discovery of lysosome.
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Fujishiro-dai, Suita, Osaka, Japan. stakeda@ri.ncvc.go.jp
authors.forename: Soichi
authors.initials: S
authors.lastname: Takeda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takeya
authors.forename: Sadaaki
authors.initials: S
authors.lastname: Iwanaga
mesh_terms: D051722:ADAM Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D006801:Humans; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D045726:Metalloproteases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D008958:Models, Molecular; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs / Q000235:genetics / Q000502:physiology; D012910:Snake Venoms / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship
chemical_list: D012910:Snake Venoms; D045726:Metalloproteases; D051722:ADAM Proteins