2clm

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TRYPTOPHAN SYNTHASE (EXTERNAL ALDIMINE STATE) IN COMPLEX WITH N-(4'-TRIFLUOROMETHOXYBENZOYL)-2-AMINO-1-ETHYLPHOSPHATE (F6F)

Structural highlights

2clm is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:F6F, NA, PLS
Activity:Tryptophan synthase, with EC number 4.2.1.20
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[TRPA_SALTY] The alpha subunit is responsible for the aldol cleavage of indoleglycerol phosphate to indole and glyceraldehyde 3-phosphate. [TRPB_SALTY] The beta subunit is responsible for the synthesis of L-tryptophan from indole and L-serine.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

In the tryptophan synthase bienzyme complex, indole produced by substrate cleavage at the alpha-site is channeled to the beta-site via a 25 A long tunnel. Within the beta-site, indole and l-Ser react with pyridoxal 5'-phosphate in a two-stage reaction to give l-Trp. In stage I, l-Ser forms an external aldimine, E(Aex1), which converts to the alpha-aminoacrylate aldimine, E(A-A). Formation of E(A-A) at the beta-site activates the alpha-site >30-fold. In stage II, indole reacts with E(A-A) to give l-Trp. The binding of alpha-site ligands (ASLs) exerts strong allosteric effects on the reaction of substrates at the beta-site: the distribution of intermediates formed in stage I is shifted in favor of E(A-A), and the binding of ASLs triggers a conformational change in the beta-site to a state with an increased affinity for l-Ser. Here, we compare the behavior of new ASLs as allosteric effectors of stage I with the behavior of the natural product, d-glyceraldehyde 3-phosphate. Rapid kinetics and kinetic isotope effects show these ASLs bind with affinities ranging from micro- to millimolar, and the rate-determining step for conversion of E(Aex1) to E(A-A) is increased by 8-10-fold. To derive a structure-based mechanism for stage I, X-ray structures of both the E(Aex1) and E(A-A) states complexed with the different ASLs were determined and compared with structures of the ASL complexes with the internal aldimine [Ngo, H., Harris, R., Kimmich, N., Casino, P., Niks, D., Blumenstein, L., Barends, T. R., Kulik, V., Weyand, M., Schlichting, I., and Dunn, M. F. (2007) Biochemistry 46, 7713-7727].

Allosteric regulation of substrate channeling in tryptophan synthase: modulation of the L-serine reaction in stage I of the beta-reaction by alpha-site ligands.,Ngo H, Kimmich N, Harris R, Niks D, Blumenstein L, Kulik V, Barends TR, Schlichting I, Dunn MF Biochemistry. 2007 Jul 3;46(26):7740-53. Epub 2007 Jun 9. PMID:17559232[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
6 reviews cite this structure
Tryptophan synthase: the workings of a channeling nanomachine.
Dunn et al. (2008)
5 more
29 other articles
No citations found

See Also

References

  1. ↑ Ngo H, Kimmich N, Harris R, Niks D, Blumenstein L, Kulik V, Barends TR, Schlichting I, Dunn MF. Allosteric regulation of substrate channeling in tryptophan synthase: modulation of the L-serine reaction in stage I of the beta-reaction by alpha-site ligands. Biochemistry. 2007 Jul 3;46(26):7740-53. Epub 2007 Jun 9. PMID:17559232 doi:10.1021/bi7003872

Contents


2clm, resolution 1.51Å

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