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Amino acid sequence and crystal structure of BaP1, a metalloproteinase from Bothrops asper snake venom that exerts multiple tissue-damaging activities.
Structural highlights
FunctionVM1B1_BOTAS Zinc metalloprotease that exhibits a weak hemorrhagic activity (with a minimum hemorrhagic dose of 20 ug by intradermal and intramuscular injection into mice). The basal membrane components collagen (all chains of type IV) (COL4A4), laminin and nidogen are all degraded by this toxin (PubMed:23385358). Rapidly degrades the Aalpha-chain (FGA) of fibrinogen, and later on, degrades the Bbeta-chain (FGB) of fibrinogen (PubMed:7778126). Also activates the complement system, and induces rat neutrophil chemotaxis (PubMed:11200361). Induces edema in mouse food pad and a mild myotoxicity (PubMed:7778126).[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBaP1 is a 22.7-kD P-I-type zinc-dependent metalloproteinase isolated from the venom of the snake Bothrops asper, a medically relevant species in Central America. This enzyme exerts multiple tissue-damaging activities, including hemorrhage, myonecrosis, dermonecrosis, blistering, and edema. BaP1 is a single chain of 202 amino acids that shows highest sequence identity with metalloproteinases isolated from the venoms of snakes of the subfamily Crotalinae. It has six Cys residues involved in three disulfide bridges (Cys 117-Cys 197, Cys 159-Cys 181, Cys 157-Cys 164). It has the consensus sequence H(142)E(143)XXH(146)XXGXXH(152), as well as the sequence C(164)I(165)M(166), which characterize the "metzincin" superfamily of metalloproteinases. The active-site cleft separates a major subdomain (residues 1-152), comprising four alpha-helices and a five-stranded beta-sheet, from the minor subdomain, which is formed by a single alpha-helix and several loops. The catalytic zinc ion is coordinated by the N(epsilon 2) nitrogen atoms of His 142, His 146, and His 152, in addition to a solvent water molecule, which in turn is bound to Glu 143. Several conserved residues contribute to the formation of the hydrophobic pocket, and Met 166 serves as a hydrophobic base for the active-site groups. Sequence and structural comparisons of hemorrhagic and nonhemorrhagic P-I metalloproteinases from snake venoms revealed differences in several regions. In particular, the loop comprising residues 153 to 176 has marked structural differences between metalloproteinases with very different hemorrhagic activities. Because this region lies in close proximity to the active-site microenvironment, it may influence the interaction of these enzymes with physiologically relevant substrates in the extracellular matrix. Amino acid sequence and crystal structure of BaP1, a metalloproteinase from Bothrops asper snake venom that exerts multiple tissue-damaging activities.,Watanabe L, Shannon JD, Valente RH, Rucavado A, Alape-Giron A, Kamiguti AS, Theakston RD, Fox JW, Gutierrez JM, Arni RK Protein Sci. 2003 Oct;12(10):2273-81. PMID:14500885[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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