6XNC

Salmonella typhimurium tryptophan synthase complexed with L-tryptophan and D-glycerol-3-phosphate

Summary for 6XNC

• Entry DOI: 10.2210/pdb6xnc/pdb
• Descriptor: Tryptophan synthase alpha chain, Tryptophan synthase beta chain, DIMETHYL SULFOXIDE, ... (8 entities in total)
• Functional Keywords: multi-enzyme complex, allosteric enzyme product complex, lyase
• Biological source: Salmonella typhimurium (Salmonella enterica subsp. enterica serovar Typhimurium); More
• Total number of polymer chains: 2
• Total formula weight: 74451.83

Authors

Phillips, R.S. (deposition date: 2020-07-02, release date: 2021-02-03, Last modification date: 2023-10-18)

Primary citation

Phillips, R.S.,Harris, A.P.
Structural Basis of the Stereochemistry of Inhibition of Tryptophan Synthase by Tryptophan and Derivatives.
Biochemistry, 60:231-244, 2021

PubMed Abstract: We have examined the reaction of serovar typhimurium tryptophan (Trp) synthase αβ complex with l-Trp, d-Trp, oxindolyl-l-alanine (OIA), and dioxindolyl-l-alanine (DOA) in the presence of disodium (dl)-α-glycerol phosphate (GP), using stopped-flow spectrophotometry and X-ray crystallography. All structures contained the d-isomer of GP bound at the α-active site. (3)-OIA reacts with the pyridoxal-5'-phosphate (PLP) of Trp synthase to form a mixture of external aldimine and quinonoid complexes. The α-carboxylate of OIA rotates about 90° to become planar with the PLP when the quinonoid complex is formed, resulting in a conformational change in the loop of residues 110-115. The COMM domain of the Trp synthase-OIA complex is found as a mixture of two conformations. The (3)-diastereomer of DOA binds about 5-fold more tightly than (3)-OIA and also forms a mixture of aldimine and quinonoid complexes. DOA forms an additional H-bond between the 3-OH of DOA and βLys-87. l-Trp does not form a covalent complex with the PLP of Trp synthase. However, d-Trp forms a mixture of two external aldimine complexes which differ in the orientation of the α-carboxylate. In one conformation, the α-carboxylate is in the plane of the PLP, while in the other conformation, the α-carboxylate is perpendicular to the PLP plane. These results confirm that the stereochemistry of the transient indolenine quinonoid intermediate in the mechanism of Trp synthase is (3) and demonstrate the linkage between aldimine and quinonoid reaction intermediates in the β-active site and allosteric communications with the α-active site.

PubMed: 33428374
DOI: 10.1021/acs.biochem.0c00635

Experimental method

X-RAY DIFFRACTION (2.11 Å)