Sonali Dhindwal, Dipak N. Patil, Mahmood Mohammadi, Michel Sylvestre, Shailly Tomar et Pravindra Kumar
Article de revue (2011)
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Abstract
Biphenyl dehydrogenase, a member of short-chain dehydrogenase/reductase enzymes, catalyzes the second step of the biphenyl/polychlorinated biphenyls catabolic pathway in bacteria. To understand the molecular basis for the broad substrate specificity of Pandoraea pnomenusa strain B-356 biphenyl dehydrogenase (BphB(B-356)), the crystal structures of the apo-enzyme, the binary complex with NAD(+), and the ternary complexes with NAD(+)-2,3-dihydroxybiphenyl and NAD(+)-4,4'-dihydroxybiphenyl were determined at 2.2-, 2.5-, 2.4-, and 2.1-A resolutions, respectively. A crystal structure representing an intermediate state of the enzyme was also obtained in which the substrate binding loop was ordered as compared with the apo and binary forms but it was displaced significantly with respect to the ternary structures. These five structures reveal that the substrate binding loop is highly mobile and that its conformation changes during ligand binding, starting from a disorganized loop in the apo state to a well organized loop structure in the ligand-bound form. Conformational changes are induced during ligand binding; forming a well defined cavity to accommodate a wide variety of substrates. This explains the biochemical data that shows BphB(B-356) converts the dihydrodiol metabolites of 3,3'-dichlorobiphenyl, 2,4,4'-trichlorobiphenyl, and 2,6-dichlorobiphenyl to their respective dihydroxy metabolites. For the first time, a combination of structural, biochemical, and molecular docking studies of BphB(B-356) elucidate the unique ability of the enzyme to transform the cis-dihydrodiols of double meta-, para-, and ortho-substituted chlorobiphenyls.
Mots clés
Bacterial Proteins/*chemistry; Burkholderiaceae/*enzymology; Chlorophenols/chemistry; Crystallography, X-Ray; Ligands; Oxidoreductases/*chemistry; Protein Structure, Quaternary; Protein Structure, Secondary; Protein Structure, Tertiary; Structure-Activity Relationship; Substrate Specificity;
Sujet(s): | 1800 Génie chimique > 1802 Génie biochimique |
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Département: |
Département de génie informatique et génie logiciel Institut de génie biomédical |
Organismes subventionnaires: | Department of Biotechnology (DBT), India |
URL de PolyPublie: | https://publications.polymtl.ca/10623/ |
Édition: | 2011/09/02e éd. |
Titre de la revue: | Journal of Biological Chemistry (vol. 286, no 42) |
Maison d'édition: | Science Direct |
DOI: | 10.1074/jbc.m111.291013 |
URL officielle: | https://doi.org/10.1074/jbc.m111.291013 |
Date du dépôt: | 01 mars 2023 14:23 |
Dernière modification: | 09 avr. 2024 00:11 |
Citer en APA 7: | Dhindwal, S., Patil, D. N., Mohammadi, M., Sylvestre, M., Tomar, S., & Kumar, P. (2011). Biochemical Studies and Ligand-bound Structures of Biphenyl Dehydrogenase from Pandoraea pnomenusa Strain B-356 Reveal a Basis for Broad Specificity of the Enzyme. Journal of Biological Chemistry, 286(42), 37011-37022. https://doi.org/10.1074/jbc.m111.291013 |
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