6xnc
Salmonella typhimurium tryptophan synthase complexed with L-tryptophan and D-glycerol-3-phosphate
Structural highlights
FunctionTRPA_SALTY The alpha subunit is responsible for the aldol cleavage of indoleglycerol phosphate to indole and glyceraldehyde 3-phosphate. Publication Abstract from PubMedWe have examined the reaction of Salmonella enterica serovar typhimurium tryptophan (Trp) synthase alpha(2)beta(2) complex with l-Trp, d-Trp, oxindolyl-l-alanine (OIA), and dioxindolyl-l-alanine (DOA) in the presence of disodium (dl)-alpha-glycerol phosphate (GP), using stopped-flow spectrophotometry and X-ray crystallography. All structures contained the d-isomer of GP bound at the alpha-active site. (3S)-OIA reacts with the pyridoxal-5'-phosphate (PLP) of Trp synthase to form a mixture of external aldimine and quinonoid complexes. The alpha-carboxylate of OIA rotates about 90 degrees 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 (3R)-diastereomer of DOA binds about 5-fold more tightly than (3S)-OIA and also forms a mixture of aldimine and quinonoid complexes. DOA forms an additional H-bond between the 3-OH of DOA and betaLys-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 alpha-carboxylate. In one conformation, the alpha-carboxylate is in the plane of the PLP, while in the other conformation, the alpha-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 (3S) and demonstrate the linkage between aldimine and quinonoid reaction intermediates in the beta-active site and allosteric communications with the alpha-active site. Structural Basis of the Stereochemistry of Inhibition of Tryptophan Synthase by Tryptophan and Derivatives.,Phillips RS, Harris AP Biochemistry. 2021 Jan 26;60(3):231-244. doi: 10.1021/acs.biochem.0c00635. Epub , 2021 Jan 11. PMID:33428374[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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