Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2003-9-22
pubmed:databankReference
pubmed:abstractText
Disintegrins are a family of small proteins containing an Arg-Gly-Asp (RGD) sequence motif that binds specifically to integrin receptors. Since the integrin is known to serve as the final common pathway leading to aggregation via formation of platelet-platelet bridges, disintegrins act as fibrinogen receptor antagonists. Here, we report the first crystal structure of a disintegrin, trimestatin, found in snake venom. The structure of trimestatin at 1.7A resolution reveals that a number of turns and loops form a rigid core stabilized by six disulfide bonds. Electron densities of the RGD sequence are visible clearly at the tip of a hairpin loop, in such a manner that the Arg and Asp side-chains point in opposite directions. A docking model using the crystal structure of integrin alphaVbeta3 suggests that the Arg binds to the propeller domain, and Asp to the betaA domain. This model indicates that the C-terminal region is another potential binding site with integrin receptors. In addition to the RGD sequence, the structural evidence of a C-terminal region (Arg66, Trp67 and Asn68) important for disintegrin activity allows understanding of the high affinity and selectiveness of snake venom disintegrin for integrin receptors. The crystal structure of trimestatin should provide a useful framework for designing and developing more effective drugs for controlling platelet aggregation and anti-angiogenesis cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
332
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1115-22
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:14499613-Amino Acid Motifs, pubmed-meshheading:14499613-Amino Acid Sequence, pubmed-meshheading:14499613-Angiogenesis Inhibitors, pubmed-meshheading:14499613-Antineoplastic Agents, pubmed-meshheading:14499613-Asparagine, pubmed-meshheading:14499613-Aspartic Acid, pubmed-meshheading:14499613-Blood Platelets, pubmed-meshheading:14499613-Cell Adhesion, pubmed-meshheading:14499613-Crystallography, X-Ray, pubmed-meshheading:14499613-Disintegrins, pubmed-meshheading:14499613-Integrin alphaVbeta3, pubmed-meshheading:14499613-Integrins, pubmed-meshheading:14499613-Magnetic Resonance Spectroscopy, pubmed-meshheading:14499613-Models, Molecular, pubmed-meshheading:14499613-Molecular Sequence Data, pubmed-meshheading:14499613-Neoplasms, pubmed-meshheading:14499613-Oligopeptides, pubmed-meshheading:14499613-Platelet Aggregation, pubmed-meshheading:14499613-Protein Binding, pubmed-meshheading:14499613-Protein Structure, Tertiary, pubmed-meshheading:14499613-Sequence Homology, Amino Acid, pubmed-meshheading:14499613-Snake Venoms, pubmed-meshheading:14499613-Tryptophan
pubmed:year
2003
pubmed:articleTitle
Crystal structure of trimestatin, a disintegrin containing a cell adhesion recognition motif RGD.
pubmed:affiliation
Department of Biochemistry, National Institute of Agrobiological Sciences, 2-1-2 Kannondai, Tsukuba, Ibaraki, 305-8602, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't