Atomic resolution crystallography reveals how changes in pH shape the protein microenvironment

A.Y. Lyubimov, P.I. Lario, I. Moustafa, Alice Vrielink

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Hydrogen atoms are a vital component of enzyme structureand function1–4. In recent years, atomic resolutioncrystallography (Z1.2 A°) has been successfully used toinvestigate the role of the hydrogen atom in enzymaticcatalysis5–9. Here, atomic resolution crystallography wasused to study the effect of pH on cholesterol oxidase fromStreptomyces sp., a flavoenzyme oxidoreductase.Crystallographic observations of the anionic oxidized flavincofactor at basic pH are consistent with the UV-visibleabsorption profile of the enzyme and readily explainthe reversible pH-dependent loss of oxidation activity.Furthermore, a hydrogen atom, positioned at an unusuallyshort distance from the main chain carbonyl oxygen ofMet122 at high pH, was observed, suggesting a previouslyunknown mechanism of cofactor stabilization. This studyshows how a redox active site responds to changes in theenzyme’s environment and how these changes are able toinfluence the mechanism of enzymatic catalysis.
Original languageEnglish
Pages (from-to)259-264
JournalNature Chemical Biology
Volume2
Issue number5
DOIs
Publication statusPublished - 2006

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