Dynamic Conformational States Dictate Selectivity toward the Native Substrate in a Substrate-Permissive Acyltransferase

Levsh, Olesya; Chiang, Ying-Chih; Tung, Chun Fai; Noel, Joseph P.; Wang, Yi; Weng, Jing-Ke

doi:10.1021/acs.biochem.6b00887

Title: Dynamic Conformational States Dictate Selectivity toward the Native Substrate in a Substrate-Permissive Acyltransferase

Journal Article · Wed Nov 02 00:00:00 EDT 2016 · Biochemistry

DOI:https://doi.org/10.1021/acs.biochem.6b00887· OSTI ID:1353237

Levsh, Olesya ^[1]; Chiang, Ying-Chih ^[2]; Tung, Chun Fai ^[2]; Noel, Joseph P. ^[3]; Wang, Yi ^[2]; Weng, Jing-Ke ^[1]

Whitehead Institute for Biomedical Research, Cambridge, MA (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
The Chinese Univ. of Hong Kong (China)
Howard Hughes Medical Inst., Jack H. Skirball Center for Chemical Biology & Proteomics, The Salk Inst. for Biological Studies, La Jolla, CA (United States)

Hydroxycinnamoyl-CoA:shikimate hydroxycinnamoyltransferase (HCT) is an essential acyltransferase that mediates flux through plant phenylpropanoid metabolism by catalyzing a reaction between p-coumaroyl-CoA and shikimate, yet it also exhibits broad substrate permissiveness in vitro. How do enzymes like HCT avoid functional derailment by cellular metabolites that qualify as non-native substrates? Here, we combine X-ray crystallography and molecular dynamics to reveal distinct dynamic modes of HCT under native and non-native catalysis. We find that essential electrostatic and hydrogen-bonding interactions between the ligand and active site residues, permitted by active site plasticity, are elicited more effectively by shikimate than by other non-native substrates. This work provides a structural basis for how dynamic conformational states of HCT favor native over non-native catalysis by reducing the number of futile encounters between the enzyme and shikimate.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02–06CH11357

OSTI ID:: 1353237

Journal Information:: Biochemistry, Vol. 55, Issue 45; ISSN 0006-2960

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 37 works

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Title: Dynamic Conformational States Dictate Selectivity toward the Native Substrate in a Substrate-Permissive Acyltransferase

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