| Structural highlights
Function
[VM1B1_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 PubMed
BaP1, a zinc-dependent endopeptidase belonging to the P-I class of snake venom metalloproteinases, exerts multiple tissue-damaging activities, leading to hemorrhage, myonecrosis, dermonecrosis, blistering, and edema. Interestingly, this metalloproteinase shows a high degree of structural homology with the catalytic domain of human adamalysins and matrix metalloproteinases, especially at the strictly conserved zinc binding motif and the so-called Met turn. This highlights BaP1 as an interesting model concerning inhibitor design for several medicinally important metalloproteinases, such as tumor necrosis factor alpha converting enzyme. Here, we report the first crystal structure of BaP1 complexed with a peptidomimetic inhibitor. Suitable crystals were obtained at four different pH values (4.6, 6.5, 7.5, and 8.0), and four high-resolution structures (1.46, 1.14, 1.08, and 1.05 A) were established. These structures and the detailed analysis of the structure-activity relationship of the bound inhibitor form a basis for the design of potent BaP1 inhibitors. The latter can be used for the treatment of local pathological effects caused by snake bites, mainly due to metalloproteinases such as BaP1. Besides, the high-resolution structure is an excellent starting point for the rational development of inhibitors for human metalloproteinases. The finding of a flexible loop region may have a great impact on further studies as to date little is known about the structural dependencies of the hemorrhagic activity of snake venom metalloproteinases.
High-Resolution Crystal Structure of the Snake Venom Metalloproteinase BaP1 Complexed with a Peptidomimetic: Insight into Inhibitor Binding.,Lingott T, Schleberger C, Gutierrez JM, Merfort I Biochemistry. 2009 Jun 15. PMID:19485419[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Farsky SH, Goncalves LR, Gutierrez JM, Correa AP, Rucavado A, Gasque P, Tambourgi DV. Bothrops asper snake venom and its metalloproteinase BaP-1 activate the complement system. Role in leucocyte recruitment. Mediators Inflamm. 2000;9(5):213-21. PMID:11200361 doi:http://dx.doi.org/10.1080/09629350020025728
- ↑ Patino AC, Pereanez JA, Nunez V, Benjumea DM, Fernandez M, Rucavado A, Sanz L, Calvete JJ. Isolation and biological characterization of Batx-I, a weak hemorrhagic and fibrinogenolytic PI metalloproteinase from Colombian Bothrops atrox venom. Toxicon. 2010 Nov;56(6):936-43. doi: 10.1016/j.toxicon.2010.06.016. Epub 2010 Jun, 30. PMID:20600221 doi:http://dx.doi.org/10.1016/j.toxicon.2010.06.016
- ↑ Bernardes CP, Menaldo DL, Camacho E, Rosa JC, Escalante T, Rucavado A, Lomonte B, Gutierrez JM, Sampaio SV. Proteomic analysis of Bothrops pirajai snake venom and characterization of BpirMP, a new P-I metalloproteinase. J Proteomics. 2013 Mar 27;80:250-67. doi: 10.1016/j.jprot.2013.01.021. Epub 2013 , Feb 4. PMID:23385358 doi:http://dx.doi.org/10.1016/j.jprot.2013.01.021
- ↑ Gutierrez JM, Romero M, Diaz C, Borkow G, Ovadia M. Isolation and characterization of a metalloproteinase with weak hemorrhagic activity from the venom of the snake Bothrops asper (terciopelo). Toxicon. 1995 Jan;33(1):19-29. PMID:7778126
- ↑ Lingott T, Schleberger C, Gutierrez JM, Merfort I. High-Resolution Crystal Structure of the Snake Venom Metalloproteinase BaP1 Complexed with a Peptidomimetic: Insight into Inhibitor Binding. Biochemistry. 2009 Jun 15. PMID:19485419 doi:10.1021/bi9002315
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