KTS-去整合素对α1β1整合素选择性的结构决定因素。

Structural determinants of the selectivity of KTS-disintegrins for the alpha1beta1 integrin.

作者信息

Kisiel Dariusz G, Calvete Juan J, Katzhendler Jehoshua, Fertala Andrzej, Lazarovici Philip, Marcinkiewicz Cezary

机构信息

Center for Neurovirology and Cancer Biology, Temple University, College of Science and Technology, 1900 N., 12th Street, Philadelphia, PA 19122, USA.

出版信息

FEBS Lett. 2004 Nov 19;577(3):478-82. doi: 10.1016/j.febslet.2004.10.050.

DOI:10.1016/j.febslet.2004.10.050

PMID:15556632

Abstract

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.

摘要

KTS-去整合素是短单体去整合素的一个亚家族，是α1β1整合素的强效和选择性抑制剂。新的KTS-去整合素——蝰蛇抑制素的氨基酸序列，在第24位（整合素结合环内）、38位（疏水核心）和40位（C端区域）的三个残基上与先前鉴定的钝吻抑制素不同。值得注意的是，蝰蛇抑制素在抑制该整合素与IV型胶原结合方面的效力比钝吻抑制素高约25倍。代表这些去整合素整合素结合环全长的合成肽表明，Leu24/Arg取代似乎部分导致了蝰蛇抑制素比钝吻抑制素抑制活性增加。