Structural characterization of BRCT-tetrapeptide binding interactions

被引：14

作者：

Joseph, Prem Raj B. ^{[1
,3
]}

Yuan, Ziyan ^{[2
,5
]}

Kumar, Eric A. ^{[2
,5
]}

Lokesh, G. L. ^{[2
]}

Kizhake, Smitha ^{[2
,5
]}

Rajarathnam, Krishna ^{[1
,3
]}

Natarajan, Amarnath ^{[2
,4
,5
]}

机构：

[1] Univ Texas Galveston, Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA

[2] Univ Texas Galveston, Med Branch, Dept Pharmacol & Toxicol, Chem Biol Program, Galveston, TX 77555 USA

[3] Univ Texas Galveston, Med Branch, Sealy Ctr Struct Biol & Mol Biophys, Galveston, TX 77555 USA

[4] Univ Texas Galveston, Med Branch, Sealy Ctr Canc Cell Biol, Galveston, TX 77555 USA

[5] Univ Nebraska Med Ctr, Eppley Inst Res Canc, Omaha, NE 68198 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2010年 / 393卷 / 02期

关键词：

BRCT(BRCA1); pSXXF tetrapeptide; NMR; Structure; Thermodynamics; CYCLE CHECKPOINT CONTROL; PHOSPHOPEPTIDE RECOGNITION; BACH1; PHOSPHOPEPTIDE; DNA-REPAIR; PROTEIN; DOMAINS; REPEATS; COMPLEX;

D O I：

10.1016/j.bbrc.2010.01.098

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

BRCT(BRCA1) plays a major role in DNA repair pathway, and does so by recognizing the conserved sequence pSXXF in its target proteins. Remarkably, tetrapeptides containing pSXXF motif bind with high specificity and micromolar affinity. Here, we have characterized the binding interactions of pSXXF tetrapeptides using NMR spectroscopy and calorimetry. We show that BRCT is dynamic and becomes structured on binding, that pSer and Phe residues dictate overall binding, and that the binding affinities of the tetrapeptides are intimately linked to structural and dynamic changes both in the BRCT(BRCA1) and tetrapeptides. These results provide critical insights for designing high-affinity BRCT(BRCA1) inhibitors. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：207 / 210

页数：4

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