5T6M

Structure of the tryptophan synthase b-subunit from Pyroccus furiosus with b-methyltryptophan non-covalently bound

Summary for 5T6M

• Entry DOI: 10.2210/pdb5t6m/pdb
• Related: 5DVZ 5DW3
• Descriptor: Tryptophan synthase beta chain 1, SODIUM ION, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: tryptophan synthase, plp, non-canonical amino acid, lyase
• Biological source: Pyrococcus furiosus
• Total number of polymer chains: 4
• Total formula weight: 176476.85

Authors

Buller, A.R.,van Roye, P.,Arnold, F.H. (deposition date: 2016-09-01, release date: 2016-12-21, Last modification date: 2023-11-15)

Primary citation

Buller, A.R.,van Roye, P.,Murciano-Calles, J.,Arnold, F.H.
Tryptophan Synthase Uses an Atypical Mechanism To Achieve Substrate Specificity.
Biochemistry, 55:7043-7046, 2016

PubMed Abstract: 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 a >82000-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.

PubMed: 27935677
DOI: 10.1021/acs.biochem.6b01127

Experimental method

X-RAY DIFFRACTION (1.8 Å)