Conserved water molecules contribute to the extensive network of interactions at the active site of protein kinase A

被引:75
作者
Shaltiel, S
Cox, S
Taylor, SS [1 ]
机构
[1] Univ Calif San Diego, Sch Med, Howard Hughes Med Inst, Dept Chem & Biochem, San Diego, CA 92093 USA
[2] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel
关键词
conformational malleability; substrate recognition; protein crystallography;
D O I
10.1073/pnas.95.2.484
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Protein kinases constitute a large family of regulatory enzymes, each with a distinct specificity to restrict its action to its physiological target(s) only, The catalytic (C) subunit of protein kinase A, regarded as a structural prototype for this family, is composed of a conserved core flanked by two nonconserved segments at the amino and carboxyl termini. Here we summarize evidence to show that (i) the active site consists of an extended network of interactions that weave together both domains of the core as well as both segments that flank the core; (ii) the opening and closing of the active site cleft, including the dynamic and coordinated movement of the carboxyl terminal tail, contributes directly to substrate recognition and catalysis; and (iii) in addition to peptide and ATP, the active site contains six structured water molecules that constitute a conserved structural element of the active site, One of these active-site conserved water molecules is locked into place by its interactions with the nucleotide, the peptide substrate/inhibitor the small and large domains of the conserved core, and Tyr-330 from the carboxyl-terminal "tail.".
引用
收藏
页码:484 / 491
页数:8
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