Crystal structures of S-HPCDH reveal determinants of stereospecificity for R- and S-hydroxypropyl-coenzyme M dehydrogenases
| Autor: | Jeremy Bakelar, Dariusz A. Sliwa, Sean J. Johnson |
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| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular Stereochemistry Molecular Sequence Data Biophysics Epoxide Dehydrogenase Coenzyme M Crystallography X-Ray Biochemistry Substrate Specificity chemistry.chemical_compound Stereospecificity Oxidoreductase Catalytic Domain Xanthobacter Amino Acid Sequence Protein Structure Quaternary Molecular Biology Mesna chemistry.chemical_classification biology Chemistry Active site Substrate (chemistry) Stereoisomerism Enzyme biology.protein Protein Multimerization Oxidoreductases |
| Zdroj: | Archives of Biochemistry and Biophysics. 533:62-68 |
| ISSN: | 0003-9861 |
| DOI: | 10.1016/j.abb.2013.02.017 |
| Popis: | (R)- and (S)-hydroxypropyl-coenzyme M dehydrogenases (R- and S-HPCDH) are stereospecific enzymes that are central to the metabolism of propylene and epoxide in Xanthobacter autotrophicus. The bacterium produces R- and S-HPCDH simultaneously to facilitate transformation of R- and S-enantiomers of epoxypropane to a common achiral product 2-ketopropyl-CoM (2-KPC). Both R- and S-HPCDH are highly specific for their respective substrates as each enzyme displays less than 0.5% activity with the opposite substrate isomer. In order to elucidate the structural basis for stereospecificity displayed by R- and S-HPCDH we have determined substrate bound crystal structures of S-HPCDH to 1.6 A resolution. Comparisons to the previously reported product-bound structure of R-HPCDH reveal that although the placement of catalytic residues within the active site of each enzyme is nearly identical, structural differences in the surrounding area provide each enzyme with a distinct substrate binding pocket. These structures demonstrate how chiral discrimination by R- and S-HPCDH results from alternative binding of the distal end of substrates within each substrate binding pocket. |
| Databáze: | OpenAIRE |
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