| O2 reactivity of flavoproteins: dynamic access of dioxygen to the active site and role of a H+ relay system in D-amino acid oxidase. | |
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MedLine Citation:
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PMID: 20498362 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Molecular dynamics simulations and implicit ligand sampling methods have identified trajectories and sites of high affinity for O(2) in the protein framework of the flavoprotein D-amino-acid oxidase (DAAO). A specific dynamic channel for the diffusion of O(2) leads from solvent to the flavin Si-side (amino acid substrate and product bind on the Re-side). Based on this, amino acids that flank the putative O(2) high affinity sites have been exchanged with bulky residues to introduce steric constraints. In G52V DAAO, the valine side chain occupies the site that in wild-type DAAO has the highest O(2) affinity. In this variant, the reactivity of the reduced enzyme with O(2) is decreased >or=100-fold and the turnover number approximately 1000-fold thus verifying the concept. In addition, the simulations have identified a chain of three water molecules that might serve in relaying a H(+) from the product imino acid =NH(2)(+) group bound on the flavin Re-side to the developing peroxide on the Si-side. This function would be comparable with that of a similarly located histidine in the flavoprotein glucose oxidase. |
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Authors:
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Jan Saam; Elena Rosini; Gianluca Molla; Klaus Schulten; Loredano Pollegioni; Sandro Ghisla |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-05-24 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-02 Completed Date: 2010-09-20 Revised Date: 2011-08-25 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 24439-46 Citation Subset: IM |
Affiliation:
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Beckman Institute, University of Illinois, Urbana, Illinois 61801, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Biochemistry
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methods Catalytic Domain D-Amino-Acid Oxidase / chemistry* Flavoproteins / chemistry* Glucose Oxidase / chemistry Histidine / chemistry Imino Acids / chemistry Models, Molecular Oxidoreductases / chemistry Oxygen / chemistry* Protons* Rhodotorula / enzymology Signal Transduction Valine / chemistry Water / chemistry |
| Grant Support | |
ID/Acronym/Agency:
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P41-RR005969/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Flavoproteins; 0/Imino Acids; 0/Protons; 7004-03-7/Valine; 71-00-1/Histidine; 7732-18-5/Water; 7782-44-7/Oxygen; EC 1.-/Oxidoreductases; EC 1.1.3.4/Glucose Oxidase; EC 1.4.3.3/D-Amino-Acid Oxidase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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