Structural highlights
Publication Abstract from PubMed
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.
Dynamic Conformational States Dictate Selectivity toward the Native Substrate in a Substrate-Permissive Acyltransferase.,Levsh O, Chiang YC, Tung CF, Noel JP, Wang Y, Weng JK Biochemistry. 2016 Nov 2. PMID:27805809[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Levsh O, Chiang YC, Tung CF, Noel JP, Wang Y, Weng JK. Dynamic Conformational States Dictate Selectivity toward the Native Substrate in a Substrate-Permissive Acyltransferase. Biochemistry. 2016 Nov 2. PMID:27805809 doi:http://dx.doi.org/10.1021/acs.biochem.6b00887
