PDBsum entry 3hx9

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
101 a.a. *
HEM ×4
_CL ×2
Waters ×123
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Structure of heme-degrader, mhud (rv3592), from mycobacterium tuberculosis with two hemes bound in its active site
Structure: Protein rv3592. Chain: a, b. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Strain: h37rv. Gene: mt3698, rv3592, tb11.2. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.75Å     R-factor:   0.189     R-free:   0.231
Authors: N.Chim,T.Q.Nguyen,A.Iniguez,C.W.Goulding
Key ref: N.Chim et al. (2010). Unusual diheme conformation of the heme-degrading protein from Mycobacterium tuberculosis. J Mol Biol, 395, 595-608. PubMed id: 19917297
19-Jun-09     Release date:   01-Dec-09    
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Protein chains
P9WKH3  (MHUD_MYCTU) -  Heme-degrading monooxygenase HmoB
105 a.a.
101 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Heme oxygenase (biliverdin-producing).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
+ 3 × AH(2)
+ 3 × O(2)
= biliverdin
+ Fe(2+)
+ CO
+ 3 × A
+ 3 × H(2)O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   1 term 
  Biochemical function     oxidoreductase activity     4 terms  


J Mol Biol 395:595-608 (2010)
PubMed id: 19917297  
Unusual diheme conformation of the heme-degrading protein from Mycobacterium tuberculosis.
N.Chim, A.Iniguez, T.Q.Nguyen, C.W.Goulding.
Heme degradation plays a pivotal role in the availability of the essential nutrient, iron, in pathogenic bacteria. A previously unannotated protein from Mycobacterium tuberculosis, Rv3592, which shares homology to heme-degrading enzymes, has been identified. Biochemical analyses confirm that Rv3592, which we have termed MhuD (mycobacterial heme utilization, degrader), is able to bind and degrade heme. Interestingly, contrary to previously reported stoichiometry for the Staphylococcus aureus heme degraders, iron-regulated surface determinant (Isd)G and IsdI, MhuD has the ability to bind heme in a 1:2 protein-to-heme ratio, although the MhuD-diheme complex is inactive. Furthermore, the 1.75-A crystal structure of the MhuD-diheme complex reveals two stacked hemes forming extensive contacts with residues in the active site. In particular, the solvent-exposed heme is axially liganded by His75 and is stacked planar upon the solvent-protected heme. The solvent-protected heme is coordinated by a chloride ion, which is, in turn, stabilized by Asn7. Structural comparison between MhuD-diheme and inactive IsdG and IsdI bound to only one highly distorted metalloporphyrin ring reveals that several residues located in alpha-helix 2 and the subsequent loop appear to be responsible for heme stoichiometric differences and suggest open and closed conformations for substrate entry and product exit.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21339081 J.A.Mayfield, C.A.Dehner, and J.L.DuBois (2011).
Recent advances in bacterial heme protein biochemistry.
  Curr Opin Chem Biol, 15, 260-266.  
21383189 M.V.Tullius, C.A.Harmston, C.P.Owens, N.Chim, R.P.Morse, L.M.McMath, A.Iniguez, J.M.Kimmey, M.R.Sawaya, J.P.Whitelegge, M.A.Horwitz, and C.W.Goulding (2011).
Discovery and characterization of a unique mycobacterial heme acquisition system.
  Proc Natl Acad Sci U S A, 108, 5051-5056.
PDB code: 3may
20969756 H.K.Janagama, S.Kumar, J.P.Bannantine, A.Kugadas, P.Jagtap, L.Higgins, B.Witthuhn, and S.Sreevatsan (2010).
Iron-sparing Response of Mycobacterium avium subsp. paratuberculosis is strain dependent.
  BMC Microbiol, 10, 268.  
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