7AC8
Molecular basis for the unique allosteric activation mechanism of the heterodimeric imidazole glycerol phosphate synthase complex.
Summary for 7AC8
| Entry DOI | 10.2210/pdb7ac8/pdb |
| Descriptor | Imidazole glycerol phosphate synthase subunit HisF, Imidazole glycerol phosphate synthase subunit HisH, [(2R,3S,4R,5R)-5-[4-aminocarbonyl-5-[(E)-[[(2R,3R,4S,5R)-3,4-bis(oxidanyl)-5-(phosphonooxymethyl)oxolan-2-yl]amino]methylideneamino]imidazol-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl dihydrogen phosphate, ... (6 entities in total) |
| Functional Keywords | enzyme regulation, allostery, ensemble model, conformational changes, hisf, hish, imidazole glycerol phosphate synthase, lyase (4.3.2.10), lyase |
| Biological source | Thermotoga maritima More |
| Total number of polymer chains | 6 |
| Total formula weight | 154809.91 |
| Authors | Sung, S.,Wilmanns, M. (deposition date: 2020-09-10, release date: 2021-05-19, Last modification date: 2024-01-31) |
| Primary citation | Wurm, J.P.,Sung, S.,Kneuttinger, A.C.,Hupfeld, E.,Sterner, R.,Wilmanns, M.,Sprangers, R. Molecular basis for the allosteric activation mechanism of the heterodimeric imidazole glycerol phosphate synthase complex. Nat Commun, 12:2748-2748, 2021 Cited by PubMed Abstract: Imidazole glycerol phosphate synthase (HisFH) is a heterodimeric bienzyme complex operating at a central branch point of metabolism. HisFH is responsible for the HisH-catalyzed hydrolysis of glutamine to glutamate and ammonia, which is then used for a cyclase reaction by HisF. The HisFH complex is allosterically regulated but the underlying mechanism is not well understood. Here, we elucidate the molecular basis of the long range, allosteric activation of HisFH. We establish that the catalytically active HisFH conformation is only formed when the substrates of both HisH and HisF are bound. We show that in this conformation an oxyanion hole in the HisH active site is established, which rationalizes the observed 4500-fold allosteric activation compared to the inactive conformation. In solution, the inactive and active conformations are in a dynamic equilibrium and the HisFH turnover rates correlate with the population of the active conformation, which is in accordance with the ensemble model of allostery. PubMed: 33980881DOI: 10.1038/s41467-021-22968-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.06 Å) |
Structure validation
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