| Structural highlights
4hpx is a 2 chain structure with sequence from "bacillus_typhimurium"_loeffler_1892 "bacillus typhimurium" loeffler 1892. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , |
| Related: | 2j9x, 1a5s, 4hn4, 4ht3 |
| Gene: | STM1727, trpA ("Bacillus typhimurium" Loeffler 1892), STM1726, trpB ("Bacillus typhimurium" Loeffler 1892) |
| Activity: | Tryptophan synthase, with EC number 4.2.1.20 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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.
Publication Abstract from PubMed
The allosteric regulation of substrate channeling in tryptophan synthase involves ligand-mediated allosteric signaling that switches the alpha- and beta-subunits between open (low activity) and closed (high activity) conformations. This switching prevents the escape of the common intermediate, indole, and synchronizes the alpha- and beta-catalytic cycles. (19)F NMR studies of bound alpha-site substrate analogues, N-(4'-trifluoromethoxybenzoyl)-2-aminoethyl phosphate (F6) and N-(4'-trifluoromethoxybenzenesulfonyl)-2-aminoethyl phosphate (F9), were found to be sensitive NMR probes of beta-subunit conformation. Both the internal and external aldimine F6 complexes gave a single bound peak at the same chemical shift, while alpha-aminoacrylate and quinonoid F6 complexes all gave a different bound peak shifted by +1.07 ppm. The F9 complexes exhibited similar behavior, but with a corresponding shift of -0.12 ppm. X-ray crystal structures show the F6 and F9 CF3 groups located at the alpha-beta subunit interface and report changes in both the ligand conformation and the surrounding protein microenvironment. Ab initio computational modeling suggests that the change in (19)F chemical shift results primarily from changes in the alpha-site ligand conformation. Structures of alpha-aminoacrylate F6 and F9 complexes and quinonoid F6 and F9 complexes show the alpha- and beta-subunits have closed conformations wherein access of ligands into the alpha- and beta-sites from solution is blocked. Internal and external aldimine structures show the alpha- and beta-subunits with closed and open global conformations, respectively. These results establish that beta-subunits exist in two global conformational states, designated open, where the beta-sites are freely accessible to substrates, and closed, where the beta-site portal into solution is blocked. Switching between these conformations is critically important for the alphabeta-catalytic cycle.
Allostery and substrate channeling in the tryptophan synthase bienzyme complex: evidence for two subunit conformations and four quaternary states.,Niks D, Hilario E, Dierkers A, Ngo H, Borchardt D, Neubauer TJ, Fan L, Mueller LJ, Dunn MF Biochemistry. 2013 Sep 17;52(37):6396-411. doi: 10.1021/bi400795e. Epub 2013 Sep , 6. PMID:23952479[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Niks D, Hilario E, Dierkers A, Ngo H, Borchardt D, Neubauer TJ, Fan L, Mueller LJ, Dunn MF. Allostery and substrate channeling in the tryptophan synthase bienzyme complex: evidence for two subunit conformations and four quaternary states. Biochemistry. 2013 Sep 17;52(37):6396-411. doi: 10.1021/bi400795e. Epub 2013 Sep , 6. PMID:23952479 doi:http://dx.doi.org/10.1021/bi400795e
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