Structural determinants of the selectivity of KTS-disintegrins for the alpha1beta1 integrin.
KTS-disintegrins are a subfamily of short monomeric disintegrins that are potent and selective inhibitors of alpha1beta1 integrin. The amino acid sequence of the new KTS-disintegrin, viperistatin, differs from previously characterized obtustatin in three residues at position 24 (within the integrin binding loop), 38 (hydrophobic core) and 40 (C-terminal region). Noteworthy, viperistatin is about 25-fold more potent than obtustatin inhibiting the binding of this integrin to collagen IV. Synthetic peptides representing the full-length of integrin-binding loops of these disintegrins showed that the Leu24/Arg substitution appears to be partly responsible for the increased inhibitory activity of viperistatin over obtustatin.
Kisiel
Dariusz G
DG
Center for Neurovirology and Cancer Biology, Temple University, College of Science and Technology, 1900 N., 12th Street, Philadelphia, PA 19122, USA.
Calvete
Juan J
JJ
Katzhendler
Jehoshua
J
Fertala
Andrzej
A
Lazarovici
Philip
P
Marcinkiewicz
Cezary
C
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001120:Arginine / Q000378:metabolism; D001665:Binding Sites; D016466:CHO Cells; D002448:Cell Adhesion; D024141:Collagen Type IV / Q000302:isolation & purification / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D019483:Disintegrins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology*; D004220:Disulfides / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D039222:Integrin alpha1beta1 / Q000037:antagonists & inhibitors*; D019169:Jurkat Cells; D020014:K562 Cells; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014757:Viper Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*
D024141:Collagen Type IV; D003470:Culture Media; D019483:Disintegrins; D004220:Disulfides; D039222:Integrin alpha1beta1; D014757:Viper Venoms; D001120:Arginine; D003545:Cysteine