2CLF

Tryptophan Synthase in complex with N-(4'-trifluoromethoxybenzoyl)-2- amino-1-ethylphosphate (F6) - highF6 complex

Summary for 2CLF

• Entry DOI: 10.2210/pdb2clf/pdb
• Related: 1A50 1A5A 1A5B 1A5S 1BKS 1C29 1C8V 1C9D 1CW2 1CX9 1FUY 1GEQ 1K3U 1K7E 1K7F 1K7X 1K8Y 1K8Z 1KFJ 1KFK 1QOP 1QOQ 1RD5 1TJP 1TTP 1TTQ 1UBS 1UJP 1V7Y 1V8Z 1WBJ 1WQ5 1WXJ 1XC4 1XCF 2CLE 2CLH 2CLI 2CLK 2CLL 2CLM 2CLO 2TRS 2TSY 2TYS 2WSY
• Descriptor: TRYPTOPHAN SYNTHASE ALPHA CHAIN, TRYPTOPHAN SYNTHASE BETA CHAIN, 2-{[4-(TRIFLUOROMETHOXY)BENZOYL]AMINO}ETHYL DIHYDROGEN PHOSPHATE, ... (6 entities in total)
• Functional Keywords: aromatic amino acid biosynthesis, tryptophan biosynthesis, crbon- oxygen lyase, amino-acid biosynthesis, lyase, allosteric enzyme, pyridoxal phosphate
• Biological source: SALMONELLA TYPHIMURIUM; More
• Total number of polymer chains: 2
• Total formula weight: 72485.07

Authors

Ngo, H.,Harris, R.,Kimmich, N.,Casino, P.,Niks, D.,Blumenstein, L.,Barends, T.R.,Kulik, V.,Weyand, M.,Schlichting, I.,Dunn, M.F. (deposition date: 2006-04-27, release date: 2007-06-26, Last modification date: 2011-07-13)

Primary citation

Ngo, H.,Harris, R.,Kimmich, N.,Casino, P.,Niks, D.,Blumenstein, L.,Barends, T.R.,Kulik, V.,Weyand, M.,Schlichting, I.,Dunn, M.F.
Synthesis and Characterization of Allosteric Probes of Substrate Channeling in the Tryptophan Synthase Bienzyme Complex.
Biochemistry, 46:7713-, 2007

PubMed Abstract: Allosteric interactions regulate substrate channeling in Salmonella typhimurium tryptophan synthase. The channeling of indole between the alpha- and beta-sites via the interconnecting 25 A tunnel is regulated by allosteric signaling arising from binding of ligand to the alpha-site, and covalent reaction of l-Ser at the beta-site. This signaling switches the alpha- and beta-subunits between open conformations of low activity and closed conformations of high activity. Our objective is to synthesize and characterize new classes of alpha-site ligands (ASLs) that mimic the binding of substrates, 3-indole-d-glycerol 3'-phosphate (IGP) or d-glyceraldehyde 3-phosphate (G3P), for use in the investigation of alpha-site-beta-site interactions. The new synthesized IGP analogues contain an aryl group linked to an O-phosphoethanolamine moiety through amide, sulfonamide, or thiourea groups. The G3P analogue, thiophosphoglycolohydroxamate, contains a hydroxamic acid group linked to a thiophosphate moiety. Crystal structures of the internal aldimine complexed with G3P and with three of the new ASLs are presented. These structural and solution studies of the ASL complexes with the internal aldimine form of the enzyme establish the following. (1) ASL binding occurs with high specificity and relatively high affinities at the alpha-site. (2) Binding of the new ASLs slows the entry of indole analogues into the beta-site by blocking the tunnel opening at the alpha-site. (3) ASL binding stabilizes the closed conformations of the beta-subunit for the alpha-aminoacrylate and quinonoid forms of the enzyme. (4) The new ASLs exhibit allosteric properties that parallel the behaviors of IGP and G3P.

PubMed: 17559195
DOI: 10.1021/BI700385F

Experimental method

X-RAY DIFFRACTION (1.7 Å)