9ti2 | pdb_00009ti2

Crystal structure of the zinc-containing Phosphotriesterase dPTE2-H55(pi)MH

spinqualitylabelsall models 9ti2, resolution 1.69Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ti2 is a 6 chain structure with sequence from Brevundimonas diminuta. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.69Å Ligands: EDO, KCX, MHS, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function OPD_BREDI Has an unusual substrate specificity for synthetic organophosphate triesters and phosphorofluoridates. All of the phosphate triesters found to be substrates are synthetic compounds. The identity of any naturally occurring substrate for the enzyme is unknown. Has no detectable activity with phosphate monoesters or diesters and no activity as an esterase or protease. It catalyzes the hydrolysis of the insecticide paraoxon at a rate approaching the diffusion limit and thus appears to be optimally evolved for utilizing this synthetic substrate. Publication Abstract from PubMed Hydrolytic metalloenzymes employ Lewis-acidic metal cofactors to activate water molecules, generating nucleophilic hydroxide species that facilitate catalysis. Their catalytic efficiency across a wide pH range is often governed by the protonation state of the metal-bound water, reflected in pK(a) values typically between 6.8 and 9. Modulating this parameter is key to expanding enzymatic activity for improved activity at neutral to acidic pH. Herein, we apply genetic code expansion to mutate the primary metal-coordination sphere of a model metallohydrolase: the dizinc phosphotriesterase from Pseudomonas diminuta. Substitution of the most catalytically indispensable coordinating histidine residue (H55) to N(pi)-methyl-l-histidine (piMH) resulted in substantial enzyme yields, efficient metal coordination for either Zn(2+) or Co(2+), and up to 5-fold improved tolerance to acidic conditions. Detailed mechanistic analysis revealed a systematic decrease in catalytic pK(a) and attenuation of several catalytic rate constants. These results add to the growing body of evidence demonstrating the power of ncAA-based engineering for refined tuning of enzyme properties. Catalytic pK(a) Attenuation in a Hydrolytic Metalloenzyme by Genetic Code Expansion.,Manser BP, Deliz Liang A Biochemistry. 2026 Feb 18. doi: 10.1021/acs.biochem.5c00768. PMID:41705832 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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