1fuy
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CRYSTAL STRUCTURE OF BETAA169L/BETAC170W DOUBLE MUTANT OF TRYPTOPHAN SYNTHASE COMPLEXED WITH 5-FLUORO-INDOLE-PROPANOL PHOSPHATE
OverviewOverview
We determined the 2.25 A resolution crystal structure of the, betaA169L/betaC170W mutant form of the tryptophan synthase alpha(2)beta(2), complex from Salmonella typhimurium complexed with the alpha-active site, substrate analogue 5-fluoro-indole-propanol-phosphate to identify the, structural basis for the changed kinetic properties of the mutant, (Anderson, K. S., Kim, A. Y., Quillen, J. M., Sayers, E., Yang, X. J., and, Miles, E. W. (1995) J. Biol. Chem. 270, 29936-29944). Comparison with the, wild-type enzyme showed that the betaTrp(170) side chain occludes the, tunnel connecting the alpha- and beta-active sites, explaining the, accumulation of the intermediate indole during a single enzyme turnover., To prevent a steric clash between betaLeu(169) and betaGly(135), located, in the beta-sheet of the COMM (communication) domain, (betaGly(102)-betaGly(189)), the latter reorganizes. The changed COMM, domain conformation results in a loss of the hydrogen bonding networks, between the alpha- and beta-active sites, explaining the poor activation, of the alpha-reaction upon formation of the aminoacrylate complex at the, beta-active site. The 100-fold reduced affinity for serine seems to result, from a movement of betaAsp(305) away from the beta-active site so that it, cannot interact with the hydroxyl group of a pyridoxal phosphate-bound, serine. The proposed structural dissection of the effects of each single, mutation in the betaA169L/betaC170W mutant would explain the very, different kinetics of this mutant and betaC170F.
About this StructureAbout this Structure
1FUY is a Protein complex structure of sequences from Salmonella typhimurium with NA, FIP and PLP as ligands. Active as Tryptophan synthase, with EC number 4.2.1.20 Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for the impaired channeling and allosteric inter-subunit communication in the beta A169L/beta C170W mutant of tryptophan synthase., Weyand M, Schlichting I, J Biol Chem. 2000 Dec 29;275(52):41058-63. PMID:11034989
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