CRYSTAL-STRUCTURE OF CIS-BIPHENYL-2,3-DIHYDRODIOL-2,3-DEHYDROGENASE FROM A PCB DEGRADER AT 2.0 ANGSTROM RESOLUTION

cis-Biphenyl-2,3-dihydrodiol-2,3-dehydro (BphB) is involved in the aer obic biodegradation of polychlorinated biphenyls (PCBs). The crystal s tructure of the NAD(+)-enzyme complex was determined by molecular repl acement and refined to an R-value of 17.9% at 2.0 Angstrom. As a membe r of the short-chain alcohol dehydrogenase/reductase (SDR) family, the overall protein fold and positioning of the catalytic triad in BphB a re very similar to those observed in other SDR enzymes, although small differences occur in the cofactor binding site. Modeling studies indi cate that the substrate is bound in a deep hydrophobic cleft close to the nicotinamide moiety of the NAD(+) cofactor. These studies further suggest that Asn143 is a key determinant of substrate specificity. A t wo-step reaction mechanism is proposed for cis-dihydrodiol dehydrogena ses.