PDBsum entry 4ivm

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Oxidoreductase PDB id
Protein chain
464 a.a.
GOL ×2
Waters ×62
PDB id:
Name: Oxidoreductase
Title: Structure of human protoporphyrinogen ix oxidase(r59g)
Structure: Protoporphyrinogen oxidase. Chain: b. Synonym: ppo. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ppox. Expressed in: escherichia coli. Expression_system_taxid: 469008.
2.77Å     R-factor:   0.176     R-free:   0.240
Authors: Q.Xiaohong,W.Baifan
Key ref: B.Wang et al. (2013). Quantitative structural insight into human variegate porphyria disease. J Biol Chem, 288, 11731-11740. PubMed id: 23467411 DOI: 10.1074/jbc.M113.459768
23-Jan-13     Release date:   06-Mar-13    
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Protein chain
Pfam   ArchSchema ?
P50336  (PPOX_HUMAN) -  Protoporphyrinogen oxidase
477 a.a.
464 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Protoporphyrinogen oxidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Porphyrin Biosynthesis (later stages)
      Reaction: Protoporphyrinogen-IX + 3 O2 = protoporphyrin-IX + 3 H2O2
+ 3 × O(2)
= protoporphyrin-IX
+ 3 × H(2)O(2)
      Cofactor: FAD
Bound ligand (Het Group name = FAD) corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   7 terms 
  Biological process     small molecule metabolic process   8 terms 
  Biochemical function     oxidoreductase activity     3 terms  


DOI no: 10.1074/jbc.M113.459768 J Biol Chem 288:11731-11740 (2013)
PubMed id: 23467411  
Quantitative structural insight into human variegate porphyria disease.
B.Wang, X.Wen, X.Qin, Z.Wang, Y.Tan, Y.Shen, Z.Xi.
Defects in the human protoporphyrinogen oxidase (hPPO) gene, resulting in ∼50% decreased activity of hPPO, is responsible for the dominantly inherited disorder variegate porphyria (VP). To understand the molecular mechanism of VP, we employed the site-directed mutagenesis, biochemical assays, structural biology, and molecular dynamics simulation studies to investigate VP-causing hPPO mutants. We report here the crystal structures of R59Q and R59G mutants in complex with acifluorfen at a resolution of 2.6 and 2.8 Å. The r.m.s.d. of the Cα atoms of the active site structure of R59G and R59Q with respect to the wild-type was 0.20 and 0.15 Å, respectively. However, these highly similar static crystal structures of mutants with the wild-type could not quantitatively explain the observed large differences in their enzymatic activity. To understand how the hPPO mutations affect their catalytic activities, we combined molecular dynamics simulation and statistical analysis to quantitatively understand the molecular mechanism of VP-causing mutants. We have found that the probability of the privileged conformations of hPPO can be correlated very well with the kcat/Km of PPO (correlation coefficient, R(2) > 0.9), and the catalytic activity of 44 clinically reported VP-causing mutants can be accurately predicted. These results indicated that the VP-causing mutation affect the catalytic activity of hPPO by affecting the ability of hPPO to sample the privileged conformations. The current work, together with our previous crystal structure study on the wild-type hPPO, provided the quantitative structural insight into human variegate porphyria disease.