5lht | pdb_00005lht

ATP Phosphoribosyltransferase from Mycobacterium tuberculosis in complex with the allosteric activator 3-(2-Thienyl)-L-alanine

spinqualitylabelsall models 5lht, resolution 2.06Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5lht is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, SO4, TIH Activity: ATP phosphoribosyltransferase, with EC number 2.4.2.17 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [HIS1_MYCTU] Catalyzes the condensation of ATP and 5-phosphoribose 1-diphosphate to form N'-(5'-phosphoribosyl)-ATP (PR-ATP). Has a crucial role in the pathway because the rate of histidine biosynthesis seems to be controlled primarily by regulation of HisG enzymatic activity (By similarity). Publication Abstract from PubMed ATP-phosphoribosyltransferase (ATP-PRT) is a hexameric enzyme in conformational equilibrium between an open and seemingly active state and a closed and presumably inhibited form. The structure-function relationship of allosteric regulation in this system is still not fully understood. Here, we develop a screening strategy for modulators of ATP-PRT and identify 3-(2-thienyl)-L-alanine (TIH) as an allosteric activator of this enzyme. Kinetic analysis reveals co-occupancy of the allosteric sites by TIH and L-histidine. Crystallographic and native ion-mobility mass spectrometry data show that the TIH-bound activated form of the enzyme closely resembles the inhibited L-histidine-bound closed conformation, revealing the uncoupling between ATP-PRT open and closed conformations and its functional state. These findings suggest that dynamic processes are responsible for ATP-PRT allosteric regulation and that similar mechanisms might also be found in other enzymes bearing a ferredoxin-like allosteric domain.Active and inactive state ATP-phosphoribosyltransferases (ATP-PRTs) are believed to have different conformations. Here the authors show that in both states, ATP-PRT has a similar structural arrangement, suggesting that dynamic alterations are involved in ATP-PRT regulation by allosteric modulators. Uncoupling conformational states from activity in an allosteric enzyme.,Pisco JP, Chiara C, Pacholarz KJ, Garza-Garcia A, Ogrodowicz RW, Walker PA, Barran PE, Smerdon SJ, Carvalho LPS Nat Commun. 2017 Aug 7;8(1):203. doi: 10.1038/s41467-017-00224-0. PMID:28781362 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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