2009
DOI: 10.1073/pnas.0907548106
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Conformational sampling, catalysis, and evolution of the bacterial phosphotriesterase

Abstract: To efficiently catalyze a chemical reaction, enzymes are required to maintain fast rates for formation of the Michaelis complex, the chemical reaction and product release. These distinct demands could be satisfied via fluctuation between different conformational substates (CSs) with unique configurations and catalytic properties. However, there is debate as to how these rapid conformational changes, or dynamics, exactly affect catalysis. As a model system, we have studied bacterial phosphotriesterase (PTE), wh… Show more

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Cited by 115 publications
(143 citation statements)
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“…We also solved a structure of R18 with bound cacodylate, an analogue of the phosphodiester product of paraoxon hydrolysis, (1.50 Å resolution), and a structure of R18 in the absence of any ligand (1.85 Å). The binuclear metal ion centre of PTE at the active site (a-and b-sites) catalyses hydrolysis by stabilizing both the hydroxide nucleophile and the developing negative charge on the TS 23,28,32,33 . The metal ion centre also involves the carboxylation of a lysine residue 34 .…”
Section: Resultsmentioning
confidence: 99%
“…We also solved a structure of R18 with bound cacodylate, an analogue of the phosphodiester product of paraoxon hydrolysis, (1.50 Å resolution), and a structure of R18 in the absence of any ligand (1.85 Å). The binuclear metal ion centre of PTE at the active site (a-and b-sites) catalyses hydrolysis by stabilizing both the hydroxide nucleophile and the developing negative charge on the TS 23,28,32,33 . The metal ion centre also involves the carboxylation of a lysine residue 34 .…”
Section: Resultsmentioning
confidence: 99%
“…Recently, the question of how enzymes harness protein dynamics for catalytic efficiency has been revisited through structural and computational approaches (1,40). Coupled conformational substates optimized to admit or release substrates or organize the active site for catalysis have been described (41).…”
Section: Ementioning
confidence: 99%
“…For substrate-specific enzymes and their cognate substrate, the breadth of the free enzyme conformational ensemble and substrate concentration determine whether the enzymes utilize conformational selection of pre-existing states to bind substrate, or the "classic" device of induced fit, in which substrate drives formation of a conformation that is otherwise unpopulated. Examples of both are abundant (5)(6)(7)(8), although conformational selection is more difficult to detect experimentally (9). However, the specific advantages and disadvantages of conformational selection and induced fit are not defined well.…”
mentioning
confidence: 99%