Scientists reveal distinct substrate-binding mode in o-succinylbenzoyl-CoA synthetase

phys.org | 9/13/2017 | Staff
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o-Succinylbenzoyl-CoA (OSB-CoA) synthetase (MenE) is an essential enzyme in bacterial vitamin K biosynthesis and an important target in the development of new antibiotics. It is a member of the adenylating enzymes (ANL) family, which reconfigure their active site in two different active conformations, one for the adenylation half-reaction and the other for a thioesterification half-reaction, in a domain-alternation catalytic mechanism. Although several aspects of the adenylating mechanism in MenE have recently been uncovered, its thioesterification conformation remains elusive.

Using a catalytically competent Bacillus subtilis mutant protein complexed with an OSB-CoA analogue, researchers from the Hong Kong University of Science and Technology revealed a thioesterification active site specifically conserved among MenE orthologues and a substrate-binding mode distinct from those of many other acyl/aryl-CoA synthetases. Several residues that specifically contribute to the thioesterification half-reaction without affecting the adenylation half-reaction were identified, and they also observed a substantial movement of the activated succinyl group in the thioesterification half-reaction.

Findings - Journal - Biological - Chemistry - July

Their findings were published in the Journal of Biological Chemistry on July 21, 2017.

"Our findings provide new insights into the domain-alternation catalysis of a bacterial enzyme essential for vitamin K biosynthesis, and of its adenylating homologues in the ANL enzyme family," said Zhihong Guo, an associate professor at the Department of Chemistry of HKUST. "Our work validated the hypothesis that a distinct substrate...
(Excerpt) Read more at: phys.org
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