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PDBsum entry 1mhl

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protein ligands metals Protein-protein interface(s) links
Myeloperoxidase PDB id
1mhl
Jmol
Contents
Protein chains
104 a.a. *
466 a.a. *
Ligands
NAG ×4
NAG-NAG-BMA-MAN-
MAN-FUC
×2
HEM ×2
Metals
_CA ×2
_CL ×2
Waters ×421
* Residue conservation analysis
PDB id:
1mhl
Name: Myeloperoxidase
Title: Crystal structure of human myeloperoxidase isoform c crystal space group p2(1) at ph 5.5 and 20 deg c
Structure: Myeloperoxidase. Chain: a, b. Other_details: isoform c. Myeloperoxidase. Chain: c, d. Other_details: isoform c
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: blood. Cell: neutrophil. Organelle: azurophil granules. Organelle: azurophil granules
Biol. unit: Tetramer (from PQS)
Resolution:
2.25Å     R-factor:   0.160    
Authors: R.E.Fenna,J.Zeng,C.Davey
Key ref: R.Fenna et al. (1995). Structure of the green heme in myeloperoxidase. Arch Biochem Biophys, 316, 653-656. PubMed id: 7840679
Date:
09-Jun-95     Release date:   06-Jan-96    
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

 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  

 

 
    reference    
 
 
Arch Biochem Biophys 316:653-656 (1995)
PubMed id: 7840679  
 
 
Structure of the green heme in myeloperoxidase.
R.Fenna, J.Zeng, C.Davey.
 
  ABSTRACT  
 
A 3-A-resolution X-ray crystal structure of canine myeloperoxidase has previously revealed the overall structure of the molecule, including the polypeptide backbone conformation, but did not provide an unambiguous structure for the covalently bound heme. A higher resolution (2.28 A) X-ray crystal structure of human myeloperoxidase has now shown that the heme is a novel derivative of protoporphyrin IX in which three ring substituents form covalent bonds with amino acid side chains in the protein. Modified methyl groups on pyrrole rings A and C form ester linkages with glutamate 242 and aspartate 94, while a covalent bond between the vinyl group on ring A and the sulfur atom of methionine 243 results in a sulfonium ion linkage. The heme tetrapyrrole ring also shows considerable distortion from the planar conformation seen in most heme-containing proteins. The observed bending appears to result from these covalent bonds between diametrically opposed pyrrole rings A and C and the protein. Sequence comparisons suggest that the two ester linkages to the heme may also occur in other homologous mammalian peroxidases, but that the sulfonium ion linkage may be a unique feature of myeloperoxidase.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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.  
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
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.  
16476484 D.Lau, and S.Baldus (2006).
Myeloperoxidase and its contributory role in inflammatory vascular disease.
  Pharmacol Ther, 111, 16-26.  
15100225 W.Liu, C.E.Rogge, B.Bambai, G.Palmer, A.L.Tsai, and R.J.Kulmacz (2004).
Characterization of the heme environment in Arabidopsis thaliana fatty acid alpha-dioxygenase-1.
  J Biol Chem, 279, 29805-29815.  
11821421 L.A.LeBrun, U.Hoch, and P.R.Ortiz de Montellano (2002).
Autocatalytic mechanism and consequences of covalent heme attachment in the cytochrome P4504A family.
  J Biol Chem, 277, 12755-12761.  
11181641 M.L.Brennan, M.M.Anderson, D.M.Shih, X.D.Qu, X.Wang, A.C.Mehta, L.L.Lim, W.Shi, S.L.Hazen, J.S.Jacob, J.R.Crowley, J.W.Heinecke, and A.J.Lusis (2001).
Increased atherosclerosis in myeloperoxidase-deficient mice.
  J Clin Invest, 107, 419-430.  
10805914 K.Araki, and H.Takeuchi (2000).
Effects of pH and chloride concentration on resonance Raman spectra of human myeloperoxidase and Raman microspectroscopic analysis of enzyme state in azurophilic granules.
  Biopolymers, 57, 169-178.  
10679983 S.M.Wolf, R.P.Ferrari, S.Traversa, and K.Biemann (2000).
Determination of the carbohydrate composition and the disulfide bond linkages of bovine lactoperoxidase by mass spectrometry.
  J Mass Spectrom, 35, 210-217.  
10766826 T.J.Fiedler, C.A.Davey, and R.E.Fenna (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.
PDB codes: 1cxp 1d2v
10388773 B.D.Howes, C.B.Schiodt, K.G.Welinder, M.P.Marzocchi, J.G.Ma, J.Zhang, J.A.Shelnutt, and G.Smulevich (1999).
The quantum mixed-spin heme state of barley peroxidase: A paradigm for class III peroxidases.
  Biophys J, 77, 478-492.  
10358043 C.Oxvig, A.R.Thomsen, M.T.Overgaard, E.S.Sorensen, P.Højrup, M.J.Bjerrum, G.J.Gleich, and L.Sottrup-Jensen (1999).
Biochemical evidence for heme linkage through esters with Asp-93 and Glu-241 in human eosinophil peroxidase. The ester with Asp-93 is only partially formed in vivo.
  J Biol Chem, 274, 16953-16958.  
10480885 I.M.Kooter, N.Moguilevsky, A.Bollen, L.A.van der Veen, C.Otto, H.L.Dekker, and R.Wever (1999).
The sulfonium ion linkage in myeloperoxidase. Direct spectroscopic detection by isotopic labeling and effect of mutation.
  J Biol Chem, 274, 26794-26802.  
10447690 I.M.Kooter, N.Moguilevsky, A.Bollen, N.M.Sijtsema, C.Otto, H.L.Dekker, and R.Wever (1999).
Characterization of the Asp94 and Glu242 mutants in myeloperoxidase, the residues linking the heme group via ester bonds.
  Eur J Biochem, 264, 211-217.  
10021409 J.Littlechild (1999).
Haloperoxidases and their role in biotransformation reactions.
  Curr Opin Chem Biol, 3, 28-34.  
10187846 L.Fayadat, P.Niccoli-Sire, J.Lanet, and J.L.Franc (1999).
Role of heme in intracellular trafficking of thyroperoxidase and involvement of H2O2 generated at the apical surface of thyroid cells in autocatalytic covalent heme binding.
  J Biol Chem, 274, 10533-10538.  
10585414 O.M.Lardinois, K.F.Medzihradszky, and P.R.Ortiz de Montellano (1999).
Spin trapping and protein cross-linking of the lactoperoxidase protein radical.
  J Biol Chem, 274, 35441-35448.  
10647174 P.D.Barker, and S.J.Ferguson (1999).
Still a puzzle: why is haem covalently attached in c-type cytochromes?
  Structure, 7, R281-R290.  
10027928 S.V.Griffin, P.T.Chapman, E.A.Lianos, and C.M.Lockwood (1999).
The inhibition of myeloperoxidase by ceruloplasmin can be reversed by anti-myeloperoxidase antibodies.
  Kidney Int, 55, 917-925.  
  9510129 A.Taurog, and M.Wall (1998).
Proximal and distal histidines in thyroid peroxidase: relation to the alternatively spliced form, TPO-2.
  Thyroid, 8, 185-191.  
9848652 E.Chernokalskaya, A.N.Dubell, K.S.Cunningham, M.N.Hanson, R.E.Dompenciel, and D.R.Schoenberg (1998).
A polysomal ribonuclease involved in the destabilization of albumin mRNA is a novel member of the peroxidase gene family.
  RNA, 4, 1537-1548.  
9635778 N.M.Sijtsema, C.Otto, G.M.Segers-Nolten, A.J.Verhoeven, and J.Greve (1998).
Resonance Raman microspectroscopy of myeloperoxidase and cytochrome b558 in human neutrophilic granulocytes.
  Biophys J, 74, 3250-3255.  
9774411 T.D.Rae, and H.M.Goff (1998).
The heme prosthetic group of lactoperoxidase. Structural characteristics of heme l and heme l-peptides.
  J Biol Chem, 273, 27968-27977.  
9507022 W.M.Nauseef, S.J.McCormick, and M.Goedken (1998).
Coordinated participation of calreticulin and calnexin in the biosynthesis of myeloperoxidase.
  J Biol Chem, 273, 7107-7111.  
  9226221 R.S.McIntosh, and A.P.Weetman (1997).
Molecular analysis of the antibody response to thyroglobulin and thyroid peroxidase.
  Thyroid, 7, 471-487.  
8631940 L.A.Andersson, S.A.Bylkas, and A.E.Wilson (1996).
Spectral analysis of lactoperoxidase. Evidence for a common heme in mammalian peroxidases.
  J Biol Chem, 271, 3406-3412.  
  9035685 M.Bakovic, and H.B.Dunford (1996).
pH and temperature dependence of the rate of compound I formation from the reaction of prostaglandin endoperoxide synthase with hydrogen peroxide.
  Biochem Cell Biol, 74, 117-124.  
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 codes are shown on the right.