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Tryptophan synthase uses an atypical mechanism to achieve substrate specificity

Buller, Andrew R. and van Roye, Paul and Murciano-Calles, Javier and Arnold, Frances H. (2016) Tryptophan synthase uses an atypical mechanism to achieve substrate specificity. Biochemistry, 55 (51). pp. 7043-7046. ISSN 0006-2960. PMCID PMC5207025. doi:10.1021/acs.biochem.6b01127.

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Tryptophan synthase (TrpS) catalyzes the final steps in the biosynthesis of L-tryptophan from L-serine (Ser) and indole-3-glycerol phosphate (IGP). We report that native TrpS can also catalyze a productive reaction with L-threonine (Thr), leading to (2S,3S)-β-methyltryptophan. Surprisingly, β-substitution occurs in vitro with a 3.4-fold higher catalytic efficiency for Ser over Thr using saturating indole, despite >82,000-fold preference for Ser in direct competition using IGP. Structural data identify a novel product binding site and kinetic experiments clarify the atypical mechanism of specificity: Thr binds efficiently but decreases the affinity for indole and disrupts the allosteric signaling that regulates the catalytic cycle.

Item Type:Article
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URLURL TypeDescription Information CentralArticle
Buller, Andrew R.0000-0002-9635-4844
Murciano-Calles, Javier0000-0002-8667-1651
Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2016 American Chemical Society. Received: November 3, 2016; Revised: December 6, 2016; Published: December 9, 2016. The Caltech Molecular Observatory is supported by the Gordon and Betty Moore Foundation, the Beckman Institute, and the Sanofi-Aventis Bioengineering Research Program at Caltech. A.R.B is supported by a Ruth Kirschstein NIH Postdoctoral Fellowship (F32G110851) and J.M.C. is supported by the Alfonso Martín Escudero Foundation. The authors declare no competing financial interests. The coordinates for the PfTrpB structure with β-MeTrp bound are available from the RCSB Protein Data Bank at with PDB ID: 5T6M.
Funding AgencyGrant Number
Gordon and Betty Moore FoundationUNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
NIH Postdoctoral FellowshipF32G110851
Alfonso Martín Escudero FoundationUNSPECIFIED
Caltech Sanofi-Aventis Bioengineering Research ProgramUNSPECIFIED
Issue or Number:51
PubMed Central ID:PMC5207025
Record Number:CaltechAUTHORS:20161212-095113284
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Official Citation:Tryptophan Synthase Uses an Atypical Mechanism To Achieve Substrate Specificity Andrew R. Buller, Paul van Roye, Javier Murciano-Calles, and Frances H. Arnold Biochemistry 2016 55 (51), 7043-7046 DOI: 10.1021/acs.biochem.6b01127
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:72712
Deposited By: Tony Diaz
Deposited On:12 Dec 2016 18:23
Last Modified:07 Apr 2022 17:26

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