3gpr | pdb_00003gpr
Crystal structure of rhodocetin
Structural highlights
Function[SLEA_CALRH] Potent inhibitor of collagen-induced platelet aggregation. It acts by binding to the integrin alpha2A domain and blocks collagen binding to integrin alpha-2/beta-1 (ITGA2/ITGB1). The gamma/delta subunits mainly contribute to this activity.[1] [2] [3] [SLEB_CALRH] Potent inhibitor of collagen-induced platelet aggregation. It acts by binding to the integrin alpha2A domain and blocks collagen binding to integrin alpha-2/beta-1 (ITGA2/ITGB1). The gamma/delta subunits mainly contribute to this activity.[4] [5] [6] 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 PubMedThe integrin alpha2beta1 plays an important role in various pathophysiological processes, such as thrombosis, wound healing, inflammation, and metastasis. Rhodocetin, a constituent of the venom of the hemorrhagic Malayan pit viper (Calloselasma rhodostoma), is a specific alpha2beta1 integrin antagonist. To understand its molecular mode of action, its structure was studied by crystallography. Its quaternary structure in solution was also analyzed biochemically. Two novel subunits of rhodocetin were sequenced by mass spectrometry. Their integrin binding was measured by protein interaction ELISAs. Rhodocetin is a C-type lectin-like protein (CLP) consisting of four homologous, yet distinct, subunits, alpha, beta, gamma, and delta, the latter two of which have been unknown to date. With their CLP folds and loop-swapping motifs, the subunits alpha, beta and gamma, delta form two heterodimeric pairs. Uniquely, they arrange orthogonally and shape a cruciform molecule. Bearing a single unpaired cysteine residue, rhodocetin can only form covalent supramolecular complexes with a maximum aggregation number of 2, unlike many heterodimeric CLPs. Being the first heterotetrameric CLP to be crystallized, rhodocetin provides not only the prototypic molecular structure for heterotetrameric CLPs, but also a lead structure for pharmaceutical alpha2beta1 integrin antagonists. The alpha2beta1 integrin-specific antagonist rhodocetin is a cruciform, heterotetrameric molecule.,Eble JA, Niland S, Bracht T, Mormann M, Peter-Katalinic J, Pohlentz G, Stetefeld J FASEB J. 2009 Sep;23(9):2917-27. Epub 2009 Apr 15. PMID:19369383[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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