7okz

CRYSTAL STRUCTURE OF THE COFACTOR-DEVOID 1-H-3-HYDROXY-4- OXOQUINALDINE 2,4-DIOXYGENASE (HOD) CATALYTICALLY INACTIVE H251A VARIANT COMPLEXED WITH 2-METHYL- QUINOLIN-4(1H)-ONE UNDER HYPEROXIC CONDITIONS

spinqualitylabelsall models 7okz, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7okz is a 2 chain structure with sequence from Paenarthrobacter nitroguajacolicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.101Å Ligands: GOL, K, TAR, VFH Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HOD_PAENT Ring-cleaving dioxygenase involved in quinaldine degradation and utilization. Publication Abstract from PubMed Protein fold adaptation to novel enzymatic reactions is a fundamental evolutionary process. Cofactor-independent oxygenases degrading N-heteroaromatic substrates belong to the alpha/beta-hydrolase (ABH) fold superfamily that typically does not catalyze oxygenation reactions. Here, we have integrated crystallographic analyses under normoxic and hyperoxic conditions with molecular dynamics and quantum mechanical calculations to investigate its prototypic 1-H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase (HOD) member. O(2) localization to the "oxyanion hole", where catalysis occurs, is an unfavorable event and the direct competition between dioxygen and water for this site is modulated by the "nucleophilic elbow" residue. A hydrophobic pocket that overlaps with the organic substrate binding site can act as a proximal dioxygen reservoir. Freeze-trap pressurization allowed the structure of the ternary complex with a substrate analogue and O(2) bound at the oxyanion hole to be determined. Theoretical calculations reveal that O(2) orientation is coupled to the charge of the bound organic ligand. When 1-H-3-hydroxy-4-oxoquinaldine is uncharged, O(2) binds with its molecular axis along the ligand's C2-C4 direction in full agreement with the crystal structure. Substrate activation triggered by deprotonation of its 3-OH group by the His-Asp dyad, rotates O(2) by approximately 60 degrees . This geometry maximizes the charge transfer between the substrate and O(2), thus weakening the double bond of the latter. Electron density transfer to the O(2)(pi*) orbital promotes the formation of the peroxide intermediate via intersystem crossing that is rate-determining. Our work provides a detailed picture of how evolution has repurposed the ABH-fold architecture and its simple catalytic machinery to accomplish metal-independent oxygenation. Evolutionary adaptation from hydrolytic to oxygenolytic catalysis at the alpha/beta-hydrolase fold.,Bui S, Gil-Guerrero S, van der Linden P, Carpentier P, Ceccarelli M, Jambrina PG, Steiner RA Chem Sci. 2023 Sep 18;14(38):10547-10560. doi: 10.1039/d3sc03044j. eCollection , 2023 Oct 4. PMID:37799987 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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