3NKS
Structure of human protoporphyrinogen IX oxidase
Summary for 3NKS
| Entry DOI | 10.2210/pdb3nks/pdb |
| Related | 3I6D |
| Descriptor | Protoporphyrinogen oxidase, 5-[2-CHLORO-4-(TRIFLUOROMETHYL)PHENOXY]-2-NITROBENZOIC ACID, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total) |
| Functional Keywords | fad containing protein, ppo, variegate porphyria disease, vp, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Mitochondrion inner membrane; Peripheral membrane protein; Intermembrane side (By similarity): P50336 |
| Total number of polymer chains | 1 |
| Total formula weight | 52152.51 |
| Authors | Shen, Y. (deposition date: 2010-06-21, release date: 2011-04-20, Last modification date: 2023-11-01) |
| Primary citation | Qin, X.,Tan, Y.,Wang, L.,Wang, Z.,Wang, B.,Wen, X.,Yang, G.,Xi, Z.,Shen, Y. Structural insight into human variegate porphyria disease Faseb J., 25:653-664, 2011 Cited by PubMed Abstract: Human protoporphyrinogen IX oxidase (hPPO), a mitochondrial inner membrane protein, converts protoporphyrinogen IX to protoporphyrin IX in the heme biosynthetic pathway. Mutations in the hPPO gene cause the inherited human disease variegate porphyria (VP). In this study, we report the crystal structure of hPPO in complex with the coenzyme flavin adenine dinucleotide (FAD) and the inhibitor acifluorfen at a resolution of 1.9 Å. The structural and biochemical analyses revealed the molecular details of FAD and acifluorfen binding to hPPO as well as the interactions of the substrate with hPPO. Structural analysis and gel chromatography indicated that hPPO is a monomer rather than a homodimer in vitro. The founder-effect mutation R59W in VP patients is most likely caused by a severe electrostatic hindrance in the hydrophilic binding pocket involving the bulky, hydrophobic indolyl ring of the tryptophan. Forty-seven VP-causing mutations were purified by chromatography and kinetically characterized in vitro. The effect of each mutation was demonstrated in the high-resolution crystal structure. PubMed: 21048046DOI: 10.1096/fj.10-170811 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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