Geometrical control of the active site electronic structure of pyranopterin enzymes by metal-dithiolate folding: aldehyde oxidase.
Density functional calculations on geometry-optimized oxidized (Mo(VI)) and reduced (Mo(IV)) analogues of the isolated active site of aldehyde oxidase (MOP), a member of the xanthine oxidase family of pyranopterindithiolate enzymes, show that fold angle changes of the dithiolate ligand modulate the relative metal and dithiolate contributions to the frontier redox orbitals. Proton abstraction from the equatorial aqua ligand of the oxidized Mo(VI) site also flattens the metal dithiolate fold angle. It is proposed that static and/or dynamic changes in the structure of the protein surrounding the active site can induce changes in the dithiolate fold angle and thereby provide a mechanism for electronic buffering of the redox orbital, for fine-tuning the nucleophilicity of the equatorial aqua/hydroxide ligand, and for modulating the electron-transfer regeneration of the active sites of molybdenum and tungsten enzymes via a "dithiolate folding effect".
Joshi
Hemant K
HK
Department of Chemistry, The University of Arizona, Tucson, Arizona 85721, USA.
Enemark
John H
JH
D042931:Aldehyde Oxidase / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D003067:Coenzymes / Q000737:chemistry / Q000378:metabolism; D008667:Metalloproteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008982:Molybdenum / Q000737:chemistry / Q000378:metabolism; D000090006:Molybdenum Cofactors; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D011621:Pteridines / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013457:Sulfur Compounds / Q000737:chemistry / Q000378:metabolism
D042931:Aldehyde Oxidase; D003067:Coenzymes; D008667:Metalloproteins; D008982:Molybdenum; D000090006:Molybdenum Cofactors; D009942:Organometallic Compounds; D011621:Pteridines; D013457:Sulfur Compounds; C022261:molybdopterin