Kinetic and structural evidence of the alkenal/one reductase specificity of human ζ-crystallin.
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...
| Hlavní autoři: | , , , , , , |
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| Médium: | Journal article |
| Jazyk: | English |
| Vydáno: |
2011
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| _version_ | 1826298576410509312 |
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| author | Porté, S Moeini, A Reche, I Shafqat, N Oppermann, U Farrés, J Parés, X |
| author_facet | Porté, S Moeini, A Reche, I Shafqat, N Oppermann, U Farrés, J Parés, X |
| author_sort | Porté, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T04:48:58Z |
| format | Journal article |
| id | oxford-uuid:d44c8dba-02cb-41ef-8da5-e96da2d566af |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:48:58Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:d44c8dba-02cb-41ef-8da5-e96da2d566af2022-03-27T08:17:26ZKinetic and structural evidence of the alkenal/one reductase specificity of human ζ-crystallin.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d44c8dba-02cb-41ef-8da5-e96da2d566afEnglishSymplectic Elements at Oxford2011Porté, SMoeini, AReche, IShafqat, NOppermann, UFarrés, JParés, XHuman 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. |
| spellingShingle | Porté, S Moeini, A Reche, I Shafqat, N Oppermann, U Farrés, J Parés, X Kinetic and structural evidence of the alkenal/one reductase specificity of human ζ-crystallin. |
| title | Kinetic and structural evidence of the alkenal/one reductase specificity of human ζ-crystallin. |
| title_full | Kinetic and structural evidence of the alkenal/one reductase specificity of human ζ-crystallin. |
| title_fullStr | Kinetic and structural evidence of the alkenal/one reductase specificity of human ζ-crystallin. |
| title_full_unstemmed | Kinetic and structural evidence of the alkenal/one reductase specificity of human ζ-crystallin. |
| title_short | Kinetic and structural evidence of the alkenal/one reductase specificity of human ζ-crystallin. |
| title_sort | kinetic and structural evidence of the alkenal one reductase specificity of human ζ crystallin |
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