View source for 2clo

[[Image:2clo.jpg|left|200px]]<br /><applet load="2clo" size="450" color="white" frame="true" align="right" spinBox="true" 
caption="2clo, resolution 1.50&Aring;" />
'''TRYPTOPHAN SYNTHASE (EXTERNAL ALDIMINE STATE) IN COMPLEX WITH (NAPHTHALENE-2'-SULFONYL)-2-AMINO-1-ETHYLPHOSPHATE (F19)'''<br />

==Overview==
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.

==About this Structure==
2CLO 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, F19 and PLS 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] Known structural/functional Site: <scene name='pdbsite=AC1:Na Binding Site For Chain B'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CLO OCA]. 

==Reference==
Synthesis and characterization of allosteric probes of substrate channeling in the tryptophan synthase bienzyme complex., Ngo H, Harris R, Kimmich N, Casino P, Niks D, Blumenstein L, Barends TR, Kulik V, Weyand M, Schlichting I, Dunn MF, Biochemistry. 2007 Jul 3;46(26):7713-27. Epub 2007 Jun 9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17559195 17559195]
[[Category: Protein complex]]
[[Category: Salmonella typhimurium]]
[[Category: Tryptophan synthase]]
[[Category: Barends, T.R.]]
[[Category: Blumenstein, L.]]
[[Category: Dunn, M.F.]]
[[Category: Harris, R.]]
[[Category: Kimmich, N.]]
[[Category: Kulik, V.]]
[[Category: Ngo, H.]]
[[Category: Niks, D.]]
[[Category: Schlichting, I.]]
[[Category: F19]]
[[Category: NA]]
[[Category: PLS]]
[[Category: allosteric enzyme]]
[[Category: amino-acid biosynthesis]]
[[Category: aromatic amino acid biosynthesis]]
[[Category: carbon-oxygen lyase]]
[[Category: lyase]]
[[Category: pyridoxal phosphate]]
[[Category: tryptophan biosynthesis]]

''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 19:27:41 2007''