7ac8

Molecular basis for the unique allosteric activation mechanism of the heterodimeric imidazole glycerol phosphate synthase complex.

spinqualitylabelsall models 7ac8, resolution 2.06Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ac8 is a 6 chain structure with sequence from Thermotoga maritima and Thermotoga maritima MSB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.06Å Ligands: GLN, GUO, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HIS6_THEMA IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The HisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the HisH subunit.[HAMAP-Rule:MF_01013] Publication Abstract from PubMed 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. Molecular basis for the allosteric activation mechanism of the heterodimeric imidazole glycerol phosphate synthase complex.,Wurm JP, Sung S, Kneuttinger AC, Hupfeld E, Sterner R, Wilmanns M, Sprangers R Nat Commun. 2021 May 12;12(1):2748. doi: 10.1038/s41467-021-22968-6. PMID:33980881 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA