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PDBsum entry 1sqe

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protein Protein-protein interface(s) links
Structural genomics,unknown function PDB id
1sqe
Jmol
Contents
Protein chains
101 a.a. *
106 a.a. *
Waters ×231
* Residue conservation analysis
PDB id:
1sqe
Name: Structural genomics,unknown function
Title: 1.5a crystal structure of the protein pg130 from staphylococcus aureus, structural genomics
Structure: Hypothetical protein pg130. Chain: a, b. Engineered: yes
Source: Staphylococcus aureus. Organism_taxid: 1280. Strain: mu50. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
Resolution:
1.50Å     R-factor:   0.203     R-free:   0.245
Authors: R.Zhang,R.Wu,G.Joachimiak,O.Schneewind,A.Joachimiak,Midwest Center For Structural Genomics (Mcsg)
Key ref:
R.Wu et al. (2005). Staphylococcus aureus IsdG and IsdI, heme-degrading enzymes with structural similarity to monooxygenases. J Biol Chem, 280, 2840-2846. PubMed id: 15520015 DOI: 10.1074/jbc.M409526200
Date:
18-Mar-04     Release date:   03-Aug-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q99X56  (ISDI_STAAM) -  Heme oxygenase (staphylobilin-producing) 2
Seq:
Struc:
108 a.a.
101 a.a.
Protein chain
Pfam   ArchSchema ?
Q99X56  (ISDI_STAAM) -  Heme oxygenase (staphylobilin-producing) 2
Seq:
Struc:
108 a.a.
106 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.1.14.99.48  - Heme oxygenase (staphylobilin-producing).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. Protoheme + 4 AH2 + 4 O2 = 5-oxo-delta-bilirubin + Fe2+ + CO + 4 A + 4 H2O
2. Protoheme + 4 AH2 + 4 O2 = 15-oxo-beta-bilirubin + Fe2+ + CO + 4 A + 4 H2O
Protoheme
+ 4 × AH(2)
+ 4 × O(2)
= 5-oxo-delta-bilirubin
+ Fe(2+)
+ CO
+ 4 × A
+ 4 × H(2)O
Protoheme
+ 4 × AH(2)
+ 4 × O(2)
= 15-oxo-beta-bilirubin
+ Fe(2+)
+ CO
+ 4 × A
+ 4 × H(2)O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     oxidation-reduction process   3 terms 
  Biochemical function     oxidoreductase activity     7 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M409526200 J Biol Chem 280:2840-2846 (2005)
PubMed id: 15520015  
 
 
Staphylococcus aureus IsdG and IsdI, heme-degrading enzymes with structural similarity to monooxygenases.
R.Wu, E.P.Skaar, R.Zhang, G.Joachimiak, P.Gornicki, O.Schneewind, A.Joachimiak.
 
  ABSTRACT  
 
Heme-degrading enzymes are involved in human diseases ranging from stroke, cancer, and multiple sclerosis to infectious diseases such as malaria, diphtheria, and meningitis. All mammalian and microbial enzymes identified to date are members of the heme oxygenase superfamily and assume similar monomeric structures with an all alpha-helical fold. Here we describe the crystal structures of IsdG and IsdI, two heme-degrading enzymes from Staphylococcus aureus. The structures of both enzymes resemble the ferredoxin-like fold and form a beta-barrel at the dimer interface. Two large pockets found on the outside of the barrel contain the putative active sites. Sequence homologs of IsdG and IsdI were identified in multiple Gram-positive pathogens. Substitution of conserved IsdG amino acid residues either reduced or abolished heme degradation, suggesting a common catalytic mechanism. This mechanism of IsdG-mediated heme degradation may be similar to that of the structurally related monooxygenases, enzymes involved in the synthesis of antibiotics in Streptomyces. Our results imply the evolutionary adaptation of microbial enzymes to unique environments.
 
  Selected figure(s)  
 
Figure 1.
FIG. 1. The crystal structure of IsdG and IsdI. Residues fully conserved in all members of the IsdG family are shown in green, and other strongly conserved residues are shown in gray. A and B, IsdG dimer with subunit A is labeled in shades of blue, and subunit B is labeled in shades of orange.In B, the homodimer of IsdG is presented with the 2-fold axis of symmetry perpendicular to the plane of the picture in A. C and D, IsdI dimer with subunit A is labeled in shades of aqua, and subunit B is labeled in shades of pink. In D, the homodimer of IsdI is presented with the 2-fold axis of symmetry perpendicular to the plane of the picture in C. E, IsdG homodimer in the same orientation as B. F, IsdI homodimer in the same orientation as D, both showing predicted heme binding pockets. C (light gray) and N (dark gray) termini are shown along with the predicted binding sites of the heme substrate (red).
Figure 3.
FIG. 3. Comparative structural analysis of the IsdG and ActVA families of monooxygenases. A, ActVA-Orf6 homodimer with subunits shaded in blue and red. B, IsdG homodimer with subunits shaded in orange and green. C, IsdI homodimer with subunits shaded in aqua and pink. D, residues predicted to be involved in binding and oxidation of the substrate in ActVA-Orf6 (blue) that are conserved in IsdG (green) and IsdI (pink). E, residues shown to be required for oxidation of heme in IsdG (green) and the equivalent residues in IsdI (pink). ActVA-Orf6 residues that occupy a similar space as the catalytic residues of IsdG are shown in blue.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 2840-2846) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20807204 M.Ouattara, E.B.Cunha, X.Li, Y.S.Huang, D.Dixon, and Z.Eichenbaum (2010).
Shr of group A streptococcus is a new type of composite NEAT protein involved in sequestering haem from methaemoglobin.
  Mol Microbiol, 78, 739-756.  
19917297 N.Chim, A.Iniguez, T.Q.Nguyen, and C.W.Goulding (2010).
Unusual diheme conformation of the heme-degrading protein from Mycobacterium tuberculosis.
  J Mol Biol, 395, 595-608.
PDB code: 3hx9
19564607 S.Létoffé, G.Heuck, P.Delepelaire, N.Lange, and C.Wandersman (2009).
Bacteria capture iron from heme by keeping tetrapyrrol skeleton intact.
  Proc Natl Acad Sci U S A, 106, 11719-11724.  
17729271 H.J.Cho, K.J.Kim, M.H.Kim, and B.S.Kang (2008).
Structural insight of the role of the Hahella chejuensis HapK protein in prodigiosin biosynthesis.
  Proteins, 70, 257-262.
PDB code: 2jdj
18643935 M.L.Reniere, and E.P.Skaar (2008).
Staphylococcus aureus haem oxygenases are differentially regulated by iron and haem.
  Mol Microbiol, 69, 1304-1315.  
18954462 T.A.Binkowski, and A.Joachimiak (2008).
Protein functional surfaces: global shape matching and local spatial alignments of ligand binding sites.
  BMC Struct Biol, 8, 45.  
18715872 V.A.Villareal, R.M.Pilpa, S.A.Robson, E.A.Fadeev, and R.T.Clubb (2008).
The IsdC protein from Staphylococcus aureus uses a flexible binding pocket to capture heme.
  J Biol Chem, 283, 31591-31600.
PDB code: 2k78
18713745 W.C.Lee, M.L.Reniere, E.P.Skaar, and M.E.Murphy (2008).
Ruffling of metalloporphyrins bound to IsdG and IsdI, two heme-degrading enzymes in Staphylococcus aureus.
  J Biol Chem, 283, 30957-30963.
PDB codes: 2zdo 2zdp
17534527 A.Wilks, and K.A.Burkhard (2007).
Heme and virulence: how bacterial pathogens regulate, transport and utilize heme.
  Nat Prod Rep, 24, 511-522.  
17322319 C.A.Kunkle, and M.P.Schmitt (2007).
Comparative analysis of hmuO function and expression in Corynebacterium species.
  J Bacteriol, 189, 3650-3654.  
17637984 D.P.Giedroc, and A.I.Arunkumar (2007).
Metal sensor proteins: nature's metalloregulated allosteric switches.
  Dalton Trans, (), 3107-3120.  
17316683 J.D.Watson, S.Sanderson, A.Ezersky, A.Savchenko, A.Edwards, C.Orengo, A.Joachimiak, R.A.Laskowski, and J.M.Thornton (2007).
Towards fully automated structure-based function prediction in structural genomics: a case study.
  J Mol Biol, 367, 1511-1522.  
17387580 M.L.Reniere, V.J.Torres, and E.P.Skaar (2007).
Intracellular metalloporphyrin metabolism in Staphylococcus aureus.
  Biometals, 20, 333-345.  
17534530 M.Unno, T.Matsui, and M.Ikeda-Saito (2007).
Structure and catalytic mechanism of heme oxygenase.
  Nat Prod Rep, 24, 553-570.  
16718604 A.W.Maresso, and O.Schneewind (2006).
Iron acquisition and transport in Staphylococcus aureus.
  Biometals, 19, 193-203.  
17012401 A.W.Maresso, T.J.Chapa, and O.Schneewind (2006).
Surface protein IsdC and Sortase B are required for heme-iron scavenging of Bacillus anthracis.
  J Bacteriol, 188, 8145-8152.  
16933993 D.B.Friedman, D.L.Stauff, G.Pishchany, C.W.Whitwell, V.J.Torres, and E.P.Skaar (2006).
Staphylococcus aureus redirects central metabolism to increase iron availability.
  PLoS Pathog, 2, e87.  
16403788 E.Bab-Dinitz, H.Shmuely, J.Maupin-Furlow, J.Eichler, and B.Shaanan (2006).
Haloferax volcanii PitA: an example of functional interaction between the Pfam chlorite dismutase and antibiotic biosynthesis monooxygenase families?
  Bioinformatics, 22, 671-675.  
16428411 E.P.Skaar, A.H.Gaspar, and O.Schneewind (2006).
Bacillus anthracis IsdG, a heme-degrading monooxygenase.
  J Bacteriol, 188, 1071-1080.  
16952937 S.Puri, and M.R.O'Brian (2006).
The hmuQ and hmuD genes from Bradyrhizobium japonicum encode heme-degrading enzymes.
  J Bacteriol, 188, 6476-6482.  
17041042 V.J.Torres, G.Pishchany, M.Humayun, O.Schneewind, and E.P.Skaar (2006).
Staphylococcus aureus IsdB is a hemoglobin receptor required for heme iron utilization.
  J Bacteriol, 188, 8421-8429.  
16718605 Y.Yamamoto, C.Poyart, P.Trieu-Cuot, G.Lamberet, A.Gruss, and P.Gaudu (2006).
Roles of environmental heme, and menaquinone, in streptococcus agalactiae.
  Biometals, 19, 205-210.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.