Kinetic and structural evidence of the alkenal/one reductase specificity of human ζ-crystallin.

Journal article

Human ζ-crystallin is a Zn(2+)-lacking medium-chain dehydrogenase/reductase (MDR) included in the quinone oxidoreductase (QOR) family because of its activity with quinones. In the present work a novel enzymatic activity was characterized: the double bond α,β-hydrogenation of medium-chain 2-alkenals and 3-alkenones. The enzyme is especially active with lipid peroxidation products such as 4-hydroxyhexenal, and a role in their detoxification is discussed. This specificity is novel in the QOR family, and it is similar to that described in the distantly related alkenal/one reductase family. Moreover, we report the X-ray structure of ζ-crystallin, which represents the first structure solved for a tetrameric Zn(2+)-lacking MDR, and which allowed the identification of the active-site lining residues. Docking simulations suggest a role for Tyr53 and Tyr59 in catalysis. The kinetics of Tyr53Phe and Tyr59Phe mutants support the implication of Tyr53 in binding/catalysis of alkenal/one substrates, while Tyr59 is involved in the recognition of 4-OH-alkenals.

Authors: Porté, S; Moeini, A; Reche, I; Shafqat, N; Oppermann, U

• Publication status: Published
• Journal: Cellular and molecular life sciences : CMLS
• Volume: 68
• Issue: 6
• Pages: 1065-1077
• Publication date: 2011-03-01
• DOI: 10.1007/s00018-010-0508-2
• EISSN: 1420-9071
• ISSN: 1420-682X
• Language: English
• Keywords: Protein Binding; Molecular Structure; Protein Conformation; Gas Chromatography-Mass Spectrometry; Cloning, Molecular; zeta-Crystallins; DNA Primers; Kinetics; Crystallography, X-Ray; Humans; Catalysis; Aldehydes; Models, Molecular; Hydrogenation; Mutagenesis, Site-Directed; Substrate Specificity