Crystal structure of a short-chain dehydrogenase from <i>Burkholderia cenocepacia</i> J2315 in complex with NADP <sup>+</sup> and benzoic acid
Burkholderia cenocepacia is an opportunistic human pathogen that can cause lethal infections in immunocompromised individuals, particularly those with cystic fibrosis. As such, there is a critical need to identify and characterize the structure and function of enzymes that participate in the metabolic pathways of this bacterium. Here, the high-resolution X-ray crystal structure of a short-chain dehydrogenase reductase (SDR) from B. cenocepacia J2315 (BcSDR) in complex with the coenzyme NADP + and a benzoic acid ligand is presented. This protein has the conserved Rossmann fold of the SDR superfamily and the characteristic TG xxx G x G motif of the classical SDR subfamily. However, unlike classical SDRs, the active site of BcSDR has a leucine residue in place of the highly conserved and catalytically important tyrosine residue. Sequence analysis confirms that this leucine residue is conserved in this SDR across the Burkholderiales order. This suggests that BcSDR is more appropriately classified into the divergent SDR subfamily. In addition, this enzyme would necessarily employ a different enzyme mechanism to that proposed as a general mechanism for most SDRs.
Authors
- David M. Dranow (ORCID: https://orcid.org/0000-0003-1871-2455)
- Kafi K. J. Belfon (ORCID: https://orcid.org/0009-0003-9588-4290)
- Thomas E. Edwards (ORCID: https://orcid.org/0000-0002-0474-8003)
- Aniah Dawkins
- Jarrod B. French (ORCID: https://orcid.org/0000-0002-6762-1309)
- Jan Abendroth (ORCID: https://orcid.org/0000-0002-8229-3243)
- Zachary R. Turlington (ORCID: https://orcid.org/0000-0001-9560-0663)
- Ariel Abramov
- Andrew T. Torelli (ORCID: https://orcid.org/0000-0003-4130-9867)
- C L Hamilton
- Katherine A. Hicks (ORCID: https://orcid.org/0000-0002-1474-1067)
- Donald D. Lorimer (ORCID: https://orcid.org/0000-0002-9638-8083)
- L. J. Hicks (ORCID: https://orcid.org/0000-0002-2464-0948)
- Miriam Duncan
- Olive Beyer
- Isabella Hinojosa
- Xavier Martinez
- Sofia Mirabel
- Reagan Womack
- Yazmine Latimore
Institutions
- Albany State University (US)
- Oklahoma State University (US)
- Lenoir–Rhyne University (US)
- Center for Infectious Disease Research (US)
- University of Minnesota (US)
- Hampton University (US)
- University of California, Los Angeles (US)
- Hormel (United States) (US)
- College of the Sequoias (US)
- Manhattan University (US)
- University of Maryland, Baltimore County (US)
- Clemson University (US)
- Manchester University (US)
- Ithaca College (US)
- SUNY Cortland (US)
Publication Details
- Journal
- Acta Crystallographica Section F Structural Biology Communications
- Published
- 2024-11-26
- DOI
- https://doi.org/10.1107/s2053230x24011282
- Citations
- 3
- Primary Topic
- Enzyme Catalysis and Immobilization
- Type
- article
- Field-Weighted Citation Impact
- 0.70
Funders
- Directorate for Mathematical and Physical Sciences
- National Institute of Allergy and Infectious Diseases