title: Crystal structures of S-HPCDH reveal determinants of stereospecificity for R- and S-hydroxypropyl-coenzyme M dehydrogenases.
abstract: (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 1.6Å 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.
authors.affiliation: Department of Chemistry & Biochemistry, Utah State University, Logan, UT 84322-0300, USA.
authors.forename: Jeremy W
authors.initials: JW
authors.lastname: Bakelar
authors.forename: Dariusz A
authors.initials: DA
authors.lastname: Sliwa
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Johnson
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D015080:Mesna / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D013237:Stereoisomerism; D013379:Substrate Specificity; D020584:Xanthobacter / Q000201:enzymology
chemical_list: D010088:Oxidoreductases; D015080:Mesna