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PDBsum entry 1d2v

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
1d2v
Jmol
Contents
Protein chains
104 a.a. *
466 a.a. *
Ligands
SO4 ×3
HEM ×2
NAG-NAG-BMA-MAN-
MAN-FUC
×2
NAG ×4
ACT ×6
Metals
_CA ×2
_BR ×8
Waters ×831
* Residue conservation analysis
PDB id:
1d2v
Name: Oxidoreductase
Title: Crystal structure of bromide-bound human myeloperoxidase iso ph 5.5
Structure: Myeloperoxidase. Chain: a, b. Fragment: light chain. Myeloperoxidase. Chain: c, d. Fragment: heavy chain. Ec: 1.11.1.7
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: blood. Cell: neutrophil. Cell: neutrophil
Biol. unit: Tetramer (from PQS)
Resolution:
1.75Å     R-factor:   0.243     R-free:   0.296
Authors: T.J.Fiedler,C.A.Davey,R.E.Fenna
Key ref:
T.J.Fiedler et al. (2000). X-ray crystal structure and characterization of halide-binding sites of human myeloperoxidase at 1.8 A resolution. J Biol Chem, 275, 11964-11971. PubMed id: 10766826 DOI: 10.1074/jbc.275.16.11964
Date:
28-Sep-99     Release date:   24-Apr-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P05164  (PERM_HUMAN) -  Myeloperoxidase
Seq:
Struc:
 
Seq:
Struc:
745 a.a.
104 a.a.
Protein chains
Pfam   ArchSchema ?
P05164  (PERM_HUMAN) -  Myeloperoxidase
Seq:
Struc:
 
Seq:
Struc:
745 a.a.
466 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chains A, C, B, D: E.C.1.11.2.2  - Myeloperoxidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Cl- + H2O2 + H+ = HClO + H2O
Cl(-)
+ H(2)O(2)
+ H(+)
= HClO
+ H(2)O
      Cofactor: Ca(2+); Heme
Ca(2+)
Heme
Bound ligand (Het Group name = HEM) matches with 95.45% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     hypochlorous acid biosynthetic process   4 terms 
  Biochemical function     peroxidase activity     2 terms  

 

 
    Added reference    
 
 
DOI no: 10.1074/jbc.275.16.11964 J Biol Chem 275:11964-11971 (2000)
PubMed id: 10766826  
 
 
X-ray crystal structure and characterization of halide-binding sites of human myeloperoxidase at 1.8 A resolution.
T.J.Fiedler, C.A.Davey, R.E.Fenna.
 
  ABSTRACT  
 
The x-ray crystal structure of human myeloperoxidase has been extended to 1.8 A resolution, using x-ray data recorded at -180 degrees C (r = 0.197, free r = 0.239). Results confirm that the heme is covalently attached to the protein via two ester linkages between the carboxyl groups of Glu(242) and Asp(94) and modified methyl groups on pyrrole rings A and C of the heme as well as a sulfonium ion linkage between the sulfur atom of Met(243) and the beta-carbon of the vinyl group on pyrrole ring A. In the native enzyme a bound chloride ion has been identified at the amino terminus of the helix containing the proximal His(336). Determination of the x-ray crystal structure of a myeloperoxidase-bromide complex (r = 0.243, free r = 0.296) has shown that this chloride ion can be replaced by bromide. Bromide is also seen to bind, at partial occupancy, in the distal heme cavity, in close proximity to the distal His(95), where it replaces the water molecule hydrogen bonded to Gln(91). The bromide-binding site in the distal cavity appears to be the halide-binding site responsible for shifts in the Soret band of the absorption spectrum of myeloperoxidase. It is proposed that halide binding to this site inhibits the enzyme by effectively competing with H(2)O(2) for access to the distal histidine, whereas in compound I, the same site may be the halide substrate-binding site.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. Stereo view of the hydrogen bonding pattern for the five water molecules (W1-W5) inside the distal cavity. Superimposed is the F[o] F[c] bromide difference map contoured at ±4 , showing additional density at W2 corresponding to partial substitution by bromide. Small negative and larger positive features indicate a slight shift in the iron position.
Figure 5.
Fig. 5. Stereo view of the proximal helix chloride-binding site in the native MPO model. Residues 324-327 at the carboxyl terminus of the proximal helix are linked to residues 30-33 via two main chain hydrogen bonds. Superimposed is the F[o] F[c] bromide difference map contoured at 5 and 15 , showing additional density corresponding to replacement of chloride by bromide.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 11964-11971) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21401576 B.F.Bruner, E.S.Vista, D.M.Wynn, and J.A.James (2011).
Epitope specificity of myeloperoxidase antibodies: identification of candidate human immunodominant epitopes.
  Clin Exp Immunol, 164, 330-336.  
19768779 A.Toyama, A.Tominaga, T.Inoue, and H.Takeuchi (2010).
Activation of lactoperoxidase by heme-linked protonation and heme-independent iodide binding.
  Biopolymers, 93, 113-120.  
20544970 L.J.Smith, A.Kahraman, and J.M.Thornton (2010).
Heme proteins--diversity in structural characteristics, function, and folding.
  Proteins, 78, 2349-2368.  
19465478 A.K.Singh, N.Singh, M.Sinha, A.Bhushan, P.Kaur, A.Srinivasan, S.Sharma, and T.P.Singh (2009).
Binding modes of aromatic ligands to mammalian heme peroxidases with associated functional implications: crystal structures of lactoperoxidase complexes with acetylsalicylic acid, salicylhydroxamic acid, and benzylhydroxamic acid.
  J Biol Chem, 284, 20311-20318.  
19167310 A.K.Singh, N.Singh, S.Sharma, K.Shin, M.Takase, P.Kaur, A.Srinivasan, and T.P.Singh (2009).
Inhibition of lactoperoxidase by its own catalytic product: crystal structure of the hypothiocyanate-inhibited bovine lactoperoxidase at 2.3-A resolution.
  Biophys J, 96, 646-654.
PDB code: 3bxi
19622015 B.S.van der Veen, M.P.de Winther, and P.Heeringa (2009).
Myeloperoxidase: molecular mechanisms of action and their relevance to human health and disease.
  Antioxid Redox Signal, 11, 2899-2937.  
19669106 D.O.McDonald, and S.H.Pearce (2009).
Thyroid peroxidase forms thionamide-sensitive homodimers: relevance for immunomodulation of thyroid autoimmunity.
  J Mol Med, 87, 971-980.  
19339248 I.A.Sheikh, A.K.Singh, N.Singh, M.Sinha, S.B.Singh, A.Bhushan, P.Kaur, A.Srinivasan, S.Sharma, and T.P.Singh (2009).
Structural evidence of substrate specificity in mammalian peroxidases: structure of the thiocyanate complex with lactoperoxidase and its interactions at 2.4 A resolution.
  J Biol Chem, 284, 14849-14856.
PDB codes: 3erh 3eri 3faq
19460756 J.L.Meitzler, and P.R.Ortiz de Montellano (2009).
Caenorhabditis elegans and human dual oxidase 1 (DUOX1) "peroxidase" domains: insights into heme binding and catalytic activity.
  J Biol Chem, 284, 18634-18643.  
19817443 P.Panizzi, M.Nahrendorf, M.Wildgruber, P.Waterman, J.L.Figueiredo, E.Aikawa, J.McCarthy, R.Weissleder, and S.A.Hilderbrand (2009).
Oxazine conjugated nanoparticle detects in vivo hypochlorous acid and peroxynitrite generation.
  J Am Chem Soc, 131, 15739-15744.  
19464362 S.Galijasevic, D.Maitra, T.Lu, I.Sliskovic, I.Abdulhamid, and H.M.Abu-Soud (2009).
Myeloperoxidase interaction with peroxynitrite: chloride deficiency and heme depletion.
  Free Radic Biol Med, 47, 431-439.  
19608745 X.Carpena, P.Vidossich, K.Schroettner, B.M.Calisto, S.Banerjee, J.Stampler, M.Soudi, P.G.Furtmüller, C.Rovira, I.Fita, and C.Obinger (2009).
Essential role of proximal histidine-asparagine interaction in mammalian peroxidases.
  J Biol Chem, 284, 25929-25937.
PDB code: 3f9p
18227433 F.R.Salsbury, S.T.Knutson, L.B.Poole, and J.S.Fetrow (2008).
Functional site profiling and electrostatic analysis of cysteines modifiable to cysteine sulfenic acid.
  Protein Sci, 17, 299-312.  
18929642 G.Cheng, J.C.Salerno, Z.Cao, P.J.Pagano, and J.D.Lambeth (2008).
Identification and characterization of VPO1, a new animal heme-containing peroxidase.
  Free Radic Biol Med, 45, 1682-1694.  
18331199 M.J.Davies, C.L.Hawkins, D.I.Pattison, and M.D.Rees (2008).
Mammalian heme peroxidases: from molecular mechanisms to health implications.
  Antioxid Redox Signal, 10, 1199-1234.  
18694936 M.Ulrich, A.Petre, N.Youhnovski, F.Prömm, M.Schirle, M.Schumm, R.S.Pero, A.Doyle, J.Checkel, H.Kita, N.Thiyagarajan, K.R.Acharya, P.Schmid-Grendelmeier, H.U.Simon, H.Schwarz, M.Tsutsui, H.Shimokawa, G.Bellon, J.J.Lee, M.Przybylski, and G.Döring (2008).
Post-translational tyrosine nitration of eosinophil granule toxins mediated by eosinophil peroxidase.
  J Biol Chem, 283, 28629-28640.  
18247411 M.Zamocky, C.Jakopitsch, P.G.Furtmüller, C.Dunand, and C.Obinger (2008).
The peroxidase-cyclooxygenase superfamily: Reconstructed evolution of critical enzymes of the innate immune system.
  Proteins, 72, 589-605.  
18420576 W.M.Nauseef (2008).
Biological roles for the NOX family NADPH oxidases.
  J Biol Chem, 283, 16961-16965.  
17592500 E.Malle, P.G.Furtmüller, W.Sattler, and C.Obinger (2007).
Myeloperoxidase: a target for new drug development?
  Br J Pharmacol, 152, 838-854.  
17534531 M.Zederbauer, P.G.Furtmüller, S.Brogioni, C.Jakopitsch, G.Smulevich, and C.Obinger (2007).
Heme to protein linkages in mammalian peroxidases: impact on spectroscopic, redox and catalytic properties.
  Nat Prod Rep, 24, 571-584.  
16827659 I.I.Vlasova, J.Arnhold, A.N.Osipov, and O.M.Panasenko (2006).
pH-dependent regulation of myeloperoxidase activity.
  Biochemistry (Mosc), 71, 667-677.  
16519514 K.E.Furse, D.A.Pratt, N.A.Porter, and T.P.Lybrand (2006).
Molecular dynamics simulations of arachidonic acid complexes with COX-1 and COX-2: insights into equilibrium behavior.
  Biochemistry, 45, 3189-3205.  
15771570 A.W.Segal (2005).
How neutrophils kill microbes.
  Annu Rev Immunol, 23, 197-223.  
15747134 C.Colin, C.Leblanc, G.Michel, E.Wagner, E.Leize-Wagner, A.Van Dorsselaer, and P.Potin (2005).
Vanadium-dependent iodoperoxidases in Laminaria digitata, a novel biochemical function diverging from brown algal bromoperoxidases.
  J Biol Inorg Chem, 10, 156-166.  
16255249 M.Bakhetia, W.Charlton, H.J.Atkinson, and M.J.McPherson (2005).
RNA interference of dual oxidase in the plant nematode Meloidogyne incognita.
  Mol Plant Microbe Interact, 18, 1099-1106.  
  15238208 A.R.Cross, and A.W.Segal (2004).
The NADPH oxidase of professional phagocytes--prototype of the NOX electron transport chain systems.
  Biochim Biophys Acta, 1657, 1.  
15108282 C.Marchetti, P.Patriarca, G.P.Solero, F.E.Baralle, and M.Romano (2004).
Genetic characterization of myeloperoxidase deficiency in Italy.
  Hum Mutat, 23, 496-505.  
11468356 G.Scapin, S.Patel, V.Patel, B.Kennedy, and E.Asante-Appiah (2001).
The structure of apo protein-tyrosine phosphatase 1B C215S mutant: more than just an S --> O change.
  Protein Sci, 10, 1596-1605.
PDB code: 1i57
11589706 J.Arnhold, P.G.Furtmüller, G.Regelsberger, and C.Obinger (2001).
Redox properties of the couple compound I/native enzyme of myeloperoxidase and eosinophil peroxidase.
  Eur J Biochem, 268, 5142-5148.  
11594511 W.M.Nauseef (2001).
Contributions of myeloperoxidase to proinflammatory events: more than an antimicrobial system.
  Int J Hematol, 74, 125-133.  
11112545 P.G.Furtmüller, U.Burner, G.Regelsberger, and C.Obinger (2000).
Spectral and kinetic studies on the formation of eosinophil peroxidase compound I and its reaction with halides and thiocyanate.
  Biochemistry, 39, 15578-15584.  
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.