Show simple item record

dc.creatorLingott, Torsten
dc.creatorSchleberger, Christian
dc.creatorGutiérrez, José María
dc.creatorMerfort, Irmgard
dc.date.accessioned2016-11-16T19:38:17Z
dc.date.available2016-11-16T19:38:17Z
dc.date.issued2009-07-07
dc.identifier.citationhttp://pubs.acs.org/doi/abs/10.1021/bi9002315es_ES
dc.identifier.issn1520-4995
dc.identifier.urihttp://hdl.handle.net/10669/29255
dc.description.abstractBaP1, 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.es_ES
dc.language.isoen_USes_ES
dc.sourceBiochemistry; Volumen 48, Número 26. 2009es_ES
dc.subjectAnimalses_ES
dc.subjectBiocatalysises_ES
dc.subjectBothropses_ES
dc.subjectCatalytic Domaines_ES
dc.subjectCrystallography, X-Rayes_ES
dc.subjectHydrogen-Ion Concentrationes_ES
dc.subjectKineticses_ES
dc.subjectMetalloendopeptidaseses_ES
dc.subjectModels, Moleculares_ES
dc.subjectMolecular Structurees_ES
dc.subjectProtease Inhibitorses_ES
dc.subjectProtein Bindinges_ES
dc.subjectProtein Conformationes_ES
dc.subjectViper Venomses_ES
dc.subjectWateres_ES
dc.subjectZinces_ES
dc.subjectSnake venomes_ES
dc.titleHigh-Resolution Crystal Structure of the Snake Venom Metalloproteinase BaP1 Complexed with a Peptidomimetic: Insight into Inhibitor Bindinges_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.typeArtículo científicoes_ES
dc.identifier.doi10.1021/bi9002315
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)es_ES


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record