2WSY

CRYSTAL STRUCTURE OF WILD-TYPE TRYPTOPHAN SYNTHASE

Summary for 2WSY

• Entry DOI: 10.2210/pdb2wsy/pdb
• Descriptor: TRYPTOPHAN SYNTHASE, SODIUM ION, PYRIDOXAL-5'-PHOSPHATE, ... (4 entities in total)
• Functional Keywords: lyase, carbon-oxygen lyase, tryptophan biosynthesis, pyridoxal phosphate
• Biological source: Salmonella typhimurium; More
• Total number of polymer chains: 2
• Total formula weight: 71826.73

Authors

Schneider, T.R.,Gerhardt, E.,Lee, M.,Liang, P.-H.,Anderson, K.S.,Schlichting, I. (deposition date: 1998-02-18, release date: 1999-03-30, Last modification date: 2023-08-09)

Primary citation

Schneider, T.R.,Gerhardt, E.,Lee, M.,Liang, P.H.,Anderson, K.S.,Schlichting, I.
Loop closure and intersubunit communication in tryptophan synthase.
Biochemistry, 37:5394-5406, 1998

PubMed Abstract: Crystal structures of wild-type tryptophan synthase alpha2beta2 complexes from Salmonella typhimurium were determined to investigate the mechanism of allosteric activation of the alpha-reaction by the aminoacrylate intermediate formed at the beta-active site. Using a flow cell, the aminoacrylate (A-A) intermediate of the beta-reaction () was generated in the crystal under steady state conditions in the presence of serine and the alpha-site inhibitor 5-fluoroindole propanol phosphate (F-IPP). A model for the conformation of the Schiff base between the aminoacrylate and the beta-subunit cofactor pyridoxal phosphate (PLP) is presented. The structure is compared with structures of the enzyme determined in the absence (TRPS) and presence (TRPSF-IPP) of F-IPP. A detailed model for binding of F-IPP to the alpha-subunit is presented. In contrast to findings by Hyde et al. [(1988) J. Biol. Chem. 263,17857-17871] and Rhee et al. [(1997) Biochemistry 36, 7664-7680], we find that the presence of an alpha-site alone ligand is sufficient for loop alphaL6 closure atop the alpha-active site. Part of this loop, alphaThr183, is important not only for positioning the catalytic alphaAsp60 but also for coordinating the concomitant ordering of loop alphaL2 upon F-IPP binding. On the basis of the three structures, a pathway for communication between the alpha- and beta-active sites has been established. The central element of this pathway is a newly defined rigid, but movable, domain that on one side interacts with the alpha-subunit via loop alphaL2 and on the other side with the beta-active site. These findings provide a structural basis for understanding the allosteric properties of tryptophan synthase.

PubMed: 9548921
DOI: 10.1021/bi9728957

Experimental method

X-RAY DIFFRACTION (3.05 Å)