1a5s: Difference between revisions

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.

1A5S is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Salmonella_typhimurium Salmonella typhimurium] with NA, FIP, PLP and SER as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Tryptophan_synthase Tryptophan synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.20 4.2.1.20] Structure known Active Sites: S1 and S2. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1A5S OCA].  

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