3BHI
Crystal structure of human Carbonyl Reductase 1 in complex with NADP
Summary for 3BHI
| Entry DOI | 10.2210/pdb3bhi/pdb |
| Related | 1WMA 2PFG 3BHJ 3BHM |
| Descriptor | Carbonyl reductase [NADPH] 1, CHLORIDE ION, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total) |
| Functional Keywords | oxidoreductase, acetylation, cytoplasm, nadp, polymorphism |
| Biological source | Homo sapiens (Human) |
| Cellular location | Cytoplasm: P16152 |
| Total number of polymer chains | 1 |
| Total formula weight | 31063.61 |
| Authors | Rauh, D.,Bateman, R.L.,Shokat, K.M. (deposition date: 2007-11-28, release date: 2008-10-21, Last modification date: 2023-11-01) |
| Primary citation | Bateman, R.L.,Rauh, D.,Tavshanjian, B.,Shokat, K.M. Human carbonyl reductase 1 is an s-nitrosoglutathione reductase J.Biol.Chem., 283:35756-35762, 2008 Cited by PubMed Abstract: Human carbonyl reductase 1 (hCBR1) is an NADPH-dependent short chain dehydrogenase/reductase with broad substrate specificity and is thought to be responsible for the in vivo reduction of quinones, prostaglandins, and other carbonyl-containing compounds including xenobiotics. In addition, hCBR1 possesses a glutathione binding site that allows for increased affinity toward GSH-conjugated molecules. It has been suggested that the GSH-binding site is near the active site; however, no structures with GSH or GSH conjugates have been reported. We have solved the x-ray crystal structures of hCBR1 and a substrate mimic in complex with GSH and the catalytically inert GSH conjugate hydroxymethylglutathione (HMGSH). The structures reveal the GSH-binding site and provide insight into the affinity determinants for GSH-conjugated substrates. We further demonstrate that the structural isostere of HMGSH, S-nitrosoglutathione, is an ideal hCBR1 substrate (Km = 30 microm, kcat = 450 min(-1)) with kinetic constants comparable with the best known hCBR1 substrates. Furthermore, we demonstrate that hCBR1 dependent GSNO reduction occurs in A549 lung adenocarcinoma cell lysates and suggest that hCBR1 may be involved in regulation of tissue levels of GSNO. PubMed: 18826943DOI: 10.1074/jbc.M807125200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.27 Å) |
Structure validation
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