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Publication Abstract from PubMed

The antihemostatic/antiangiogenic protein tablysin-15 is a member of the cysteine-rich secretory, antigen 5 and pathogenesis-related 1 protein (CAP) superfamily and has been shown to bind the integrins alphaIIbbeta3 and alphaVbeta3 by means of an Arg-Gly-Asp (RGD) tripeptide sequence. Here we describe the X-ray crystal structure of tablysin-15 and show that the RGD motif is located in a novel structural context. The motif itself is contained in a type II beta-turn structure that is similar in its conformation to the RGD sequence of the cyclic pentapeptide cilengitide when bound to integrin alphaVbeta3. The CAP domain also contains a hydrophobic channel that appears to bind a fatty acid molecule in the crystal structure after purification from Escherichia coli. After delipidation of the protein, tablysin-15 was found to bind proinflammatory cysteinyl leukotrienes with submicromolar affinities. The structure of the leukotriene E4 (LTE4)-tablysin-15 complex shows that the ligand binds with the non-functionalized end of the fatty acid chain buried in the hydrophobic pocket, while the carboxylate end of the ligand binds forms hydrogen bond/salt bridge interactions with polar side chains at the channel entrance. Therefore, tablysin-15 functions as an inhibitor of integrin function and as an anti-inflammatory scavenger of eicosanoids.

Structure of a protein having inhibitory disintegrin and leukotriene scavenging functions contained in a single domain.,Xu X, Francischetti IM, Lai R, Ribeiro JM, Andersen JF J Biol Chem. 2012 Feb 6. PMID:22311975^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.