1a5s
From Proteopedia
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CRYSTAL STRUCTURE OF WILD-TYPE TRYPTOPHAN SYNTHASE COMPLEXED WITH 5-FLUOROINDOLE PROPANOL PHOSPHATE AND L-SER BOUND AS AMINO ACRYLATE TO THE BETA SITE
Overview
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.
About this Structure
1A5S is a Protein complex structure of sequences from Salmonella typhimurium with NA, FIP, PLP and SER as ligands. Active as Tryptophan synthase, with EC number 4.2.1.20 Structure known Active Sites: S1 and S2. Full crystallographic information is available from OCA.
Reference
Loop closure and intersubunit communication in tryptophan synthase., Schneider TR, Gerhardt E, Lee M, Liang PH, Anderson KS, Schlichting I, Biochemistry. 1998 Apr 21;37(16):5394-406. PMID:9548921
Page seeded by OCA on Mon Nov 5 15:45:02 2007
