Crystal Structure of Schistatin, a Disintegrin Homodimer from Saw-scaled Viper (Echis carinatus) at 2.5Å Resolution

Bilgrami, S.; Tomar, Shailly; Yadav, Savita; Kaur, Punit; Kumar, Janesh; Jabeen, T.; Sharma, Sujata

doi:10.1016/j.jmb.2004.06.048

Cited by 51 publications

(49 citation statements)

References 55 publications

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“…This situation is typical of medium-resolution NMR structures, accentuated in proteins that lack regular secondary structure. Similar Ramachandran plot statistics have been reported for the NMR structures of disintegrins flavoridin [38], echistatin [41], obtustatin [43], jerdostatin [44] and kistrin [52], as well as the Xray structure of schistatin [23].…”

Section: A Noncanonical Disulfide Bonding Pattern In Bitistatin Bsupporting

confidence: 80%

“…In addition, a number of NMR structures of medium-sized (kistrin, 1KST [53]; flavoridin, 1FVL [38]; albolabrin [39]; salmosin, 1L3X [40]; rhodostomin, 1Q7J, 1Q7I, 2PJI, 2PJF, 2PJG, 2LJV, 3UCI, 2M75, 2M7F, 2M7H) and short (echistatin, 2ECH [41]; 1RO3 [42]; obtustatin, 1MPZ [43]; jerdostatin, 2W9O, 2W9U, 2W9V, 2W9W [44]) disintegrins, and the crystal structures of the medium-sized disintegrin trimestatin (1J2L) [45] and dimeric disintegrins (schistatin, 1Z1X, 1RMR, 1TEJ [23,24]; acostatin (3CO5) [46]), have been reported. The crystal structure of the disintegrin-like and cysteine-rich domains of ADAM-10 has also been solved (2AO7) [47].…”

Section: Introductionmentioning

confidence: 99%

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NMRstructure of bitistatin – a missing piece in the evolutionary pathway of snake venom disintegrins

et al. 2014

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Extant disintegrins, as found in the venoms of Viperidae and Crotalidae snakes (vipers and rattlesnakes, represent a family of polypeptides that block the function of b1 and b3 integrin receptors, both potently and with a high degree of selectivity. This toxin family owes its origin to the neofunctionalization of the extracellular region of an ADAM (a disintegrin and metalloprotease) molecule recruited into the snake venom gland proteome in the Jurassic. The evolutionary structural diversification of the disintegrin scaffold, from the ancestral long disintegrins to the more recently evolved medium-sized, dimeric and short disintegrins, involved the stepwise loss of pairs of class-specific disulfide linkages and the processing of the N-terminal region. NMR and crystal structures of medium-sized, dimeric and short disintegrins have been solved. However, the structure of a long disintegrin remained unknown. The present study reports the NMR solution structures of two disulfide bond conformers of the long disintegrin bitistatin from the African puff adder Bitis arietans. The findings provide insight into how a structural domain of the extracellular region of an ADAM molecule, recruited into and selectively expressed in the snake venom gland proteome as a PIII metalloprotease in the Jurassic, has subsequently been tranformed into a family of integrin receptor antagonists.

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Section: A Noncanonical Disulfide Bonding Pattern In Bitistatin Bsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

NMRstructure of bitistatin – a missing piece in the evolutionary pathway of snake venom disintegrins

et al. 2014

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“…Group III is composed of homo-and heterodimers. Dimeric disintegrins contain subunits of about 67 residues with 10 cysteines involved in the formation of four intra-chain disulfide bonds and two interchain cysteine linkages (Bilgrami et al 2004(Bilgrami et al , 2005Calvete et al 2000). Group IV comprises the short disintegrins composed of 41-51 residues and four disulfide bonds.…”

Section: Classificationmentioning

confidence: 99%

Snake Venom Disintegrins

Chakrabarty¹,

Chanda²

2015

Snake Venoms

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Disintegrins are generally involved in cell-cell and cell-matrix adhesion. Although disintegrins were first identified in viper venoms, their presence in many other organs, tissues, and secretions was reported later. In snake venoms, these small cysteine-rich peptides strongly inhibit platelet aggregation and thereby antagonize clotting of blood in bite victims. The integrin binding is generally dependent upon a conserved arginine-glycine-aspartic acid (RGD) motif. However, many disintegrins lacking this RGD motif can also bind and block integrins. Disintegrins from hematophagous animals show considerable variation in the signature tripeptide disintegrin motif. However, in most cases the aspartic acid residue (D) is present. Disintegrins found in snake venoms and mammalian ADAM (disintegrin and metalloproteinase) are believed to share a common membrane-bound protein ancestor, which underwent modifications and acquired novel functions through millions of years. Recently, disintegrins have attracted researchers for their ability to strongly intervene in tumor growth and angiogenesis. Some drugs have already been designed in mimicking the molecular structures of disintegrins. Currently, many laboratories are engaged in isolating and characterizing disintegrins with a focus on developing novel anticancer and antithrombotic drugs.

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“…Unlike short-, medium-and long-sized disintegrins, which are single-chain molecules, the fifth subgroup is composed of homo and heterodimers. The dimeric disintegrins subunits contain about 67 residues with four disulfide intra-chain bridges and two interchain bridges [42,43].…”

Section: The Disintegrinsmentioning

confidence: 99%