Crystallographic and calorimetric analysis of peptide binding to OppA protein

被引:126
作者
Sleigh, SH
Seavers, PR
Wilkinson, AJ
Ladbury, JE
Tame, JRH [1 ]
机构
[1] Univ York, Dept Chem, Struct Biol Ctr, York YO10 5DD, N Yorkshire, England
[2] Univ London Univ Coll, Dept Biochem & Mol Biol, London WC1E 6BT, England
基金
英国惠康基金;
关键词
X-ray crystallography; calorimetry; peptide-binding protein; water;
D O I
10.1006/jmbi.1999.2929
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
Isothermal titration calorimetry has been used to study the binding of 20 different peptides to the peptide binding protein OppA, and the crystal structures of the ligand complexes have been refined. This periplasmic binding protein, part of the oligopeptide permease system of Gram negative bacteria, has evolved to bind and enclose small peptides of widely varying sequences. The peptides used in this study have the sequence Lys-X-Lys, where X is any of the 20 commonly occurring amino acids. The various side-chains found at position 2 on the ligand fit into a hydrated pocket. The majority of side-chains are restrained to particular conformations within the pocket. Water molecules act as flexible adapters, matching the hydrogen-bonding requirements of the protein and ligand and shielding charges on the buried ligand. This use of water by OppA to broaden the repertoire of its binding site is not unique, but contrasts sharply with other proteins which use water to help bind ligands highly selectively. Predicting the thermodynamics of binding from the structure of the complexes is highly complicated by the influence of water on the system. (C) 1999 Academic Press.
引用
收藏
页码:393 / 415
页数:23
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