Structural highlights
5bw6 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
|
| Ligands: | , , |
| Related: | 4wx2, 4y6g, 4zqc, 2clm, 2cle, 2clf |
| 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.
Publication Abstract from PubMed
Four new X-ray structures of tryptophan synthase (TS) crystallized with varying numbers of the amphipathic N-(4'-trifluoromethoxybenzoyl)-2-aminoethyl phosphate (F6) molecule are presented. These structures show one of the F6 ligands threaded into the tunnel from the beta-site and reveal a distinct hydrophobic region. Over this expanse, the interactions between F6 and the tunnel are primarily nonpolar, while the F6 phosphoryl group fits into a polar pocket of the beta-subunit active site. Further examination of TS structures reveals that one portion of the tunnel (T1) binds clusters of water molecules, whereas waters are not observed in the nonpolar F6 binding region of the tunnel (T2). MD simulation of another TS structure with an unobstructed tunnel also indicates the T2 region of the tunnel excludes water, consistent with a dewetted state that presents a significant barrier to the transfer of water into the closed beta-site. We conclude that hydrophobic molecules can freely diffuse between the alpha- and beta-sites via the tunnel, while water does not. We propose that exclusion of water serves to inhibit reaction of water with the alpha-aminoacrylate intermediate to form ammonium ion and pyruvate, a deleterious side reaction in the alphabeta-catalytic cycle. Finally, while most TS structures show betaPhe280 partially blocking the tunnel between the alpha- and beta-sites, new structures show an open tunnel, suggesting the flexibility of the betaPhe280 side chain. Flexible docking studies and MD simulations confirm that the dynamic behavior of betaPhe280 allows unhindered transfer of indole through the tunnel, therefore excluding a gating role for this residue.
Visualizing the tunnel in tryptophan synthase with crystallography: Insights into a selective filter for accommodating indole and rejecting water.,Hilario E, Caulkins BG, Huang YM, You W, Chang CE, Mueller LJ, Dunn MF, Fan L Biochim Biophys Acta. 2016 Mar;1864(3):268-79. doi: 10.1016/j.bbapap.2015.12.006., Epub 2015 Dec 17. PMID:26708480[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hilario E, Caulkins BG, Huang YM, You W, Chang CE, Mueller LJ, Dunn MF, Fan L. Visualizing the tunnel in tryptophan synthase with crystallography: Insights into a selective filter for accommodating indole and rejecting water. Biochim Biophys Acta. 2016 Mar;1864(3):268-79. doi: 10.1016/j.bbapap.2015.12.006., Epub 2015 Dec 17. PMID:26708480 doi:http://dx.doi.org/10.1016/j.bbapap.2015.12.006
