5U7E
Apo dihydroneopterin triphosphate pyrophosphohydrolase from E. coli
Summary for 5U7E
| Entry DOI | 10.2210/pdb5u7e/pdb |
| Related | 5U7F 5U7H |
| Descriptor | Dihydroneopterin triphosphate diphosphatase, SULFATE ION, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | nudix hydrolase, dihydroneopterin triphosphate pyrophosphohydrolase, hydrolase |
| Biological source | Escherichia coli O157:H7 |
| Total number of polymer chains | 1 |
| Total formula weight | 17515.89 |
| Authors | Nguyen, E.,Hill, S.E.,Lieberman, R.L. (deposition date: 2016-12-12, release date: 2017-06-21, Last modification date: 2023-10-04) |
| Primary citation | Hill, S.E.,Nguyen, E.,Ukachukwu, C.U.,Freeman, D.M.,Quirk, S.,Lieberman, R.L. Metal ion coordination in the E. coli Nudix hydrolase dihydroneopterin triphosphate pyrophosphatase: New clues into catalytic mechanism. PLoS ONE, 12:e0180241-e0180241, 2017 Cited by PubMed Abstract: Dihydroneopterin triphosphate pyrophosphatase (DHNTPase), a member of the Mg2+ dependent Nudix hydrolase superfamily, is the recently-discovered enzyme that functions in the second step of the pterin branch of the folate biosynthetic pathway in E. coli. DHNTPase is of interest because inhibition of enzymes in bacterial folate biosynthetic pathways is a strategy for antibiotic development. We determined crystal structures of DHNTPase with and without activating, Mg2+-mimicking metals Co2+ and Ni2+. Four metal ions, identified by anomalous scattering, and stoichiometrically confirmed in solution by isothermal titration calorimetry, are held in place by Glu56 and Glu60 within the Nudix sequence motif, Glu117, waters, and a sulfate ion, of which the latter is further stabilized by a salt bridge with Lys7. In silico docking of the DHNTP substrate reveals a binding mode in which the pterin ring moiety is nestled in a largely hydrophobic pocket, the β-phosphate activated for nucleophilic attack overlays with the crystallographic sulfate and is in line with an activated water molecule, and remaining phosphate groups are stabilized by all four identified metal ions. The structures and binding data provide new details regarding DHNTPase metal requirements, mechanism, and suggest a strategy for efficient inhibition. PubMed: 28742822DOI: 10.1371/journal.pone.0180241 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.942 Å) |
Structure validation
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