DB code: D00483

CATH domain 1.-.-.- : Catalytic domain
1.10.640.10 : Myeloperoxidase, subunit C Catalytic domain
E.C. 1.11.1.7
CSA 1mhl
M-CSA 1mhl
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq Pfam
P05164 Myeloperoxidase
MPO
EC 1.11.1.7
89 kDa myeloperoxidase
84 kDa myeloperoxidase
Myeloperoxidase light chain
Myeloperoxidase heavy chain
NP_000241.1 (Protein)
NM_000250.1 (DNA/RNA sequence)
PF03098 (An_peroxidase)
[Graphical View]

KEGG enzyme name
peroxidase
myeloperoxidase
lactoperoxidase
verdoperoxidase
guaiacol peroxidase
thiocyanate peroxidase
eosinophil peroxidase
Japanese radish peroxidase
horseradish peroxidase (HRP)
extensin peroxidase
heme peroxidase
MPO
oxyperoxidase
protoheme peroxidase
pyrocatechol peroxidase
scopoletin peroxidase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P05164 PERM_HUMAN Donor + H(2)O(2) = oxidized donor + 2 H(2)O. Cl(-) + H(2)O(2) = HOCl + 2 H(2)O. Tetramer of two light chains and two heavy chains. Lysosome. Binds 1 calcium ion per heterodimer. Binds 1 heme B (iron-protoporphyrin IX) group covalently per heterodimer.

KEGG Pathways
Map code Pathways E.C.
MAP00360 Phenylalanine metabolism
MAP00680 Methane metabolism
MAP00940 Phenylpropanoid biosynthesis

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00032 C00076 C01351 C00027 C00115 C02177 C00001 C99999
E.C.
Compound Heme Calcium Donor H2O2 Chloride Oxidized donor H2O Hypochlorite
Type aromatic ring (with nitrogen atoms),carboxyl group,heavy metal divalent metal (Ca2+, Mg2+) others others halide others H2O halide
ChEBI 17627
26355
17627
26355
29108
29108
16240
16240
15377
15377
PubChem 271
271
22326046
784
22326046
784
22247451
962
22247451
962
1cxpA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1cxpB Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1d2vA Unbound Unbound Unbound Unbound Analogue:_BR_843 Unbound Unbound
1d2vB Unbound Unbound Unbound Unbound Analogue:_BR_843 Unbound Unbound
1d5lA Unbound Unbound Analogue:CYN_1844 Unbound Unbound Unbound Unbound
1d5lB Unbound Unbound Analogue:CYN_1844 Unbound Unbound Unbound Unbound
1d7wA Unbound Unbound Analogue:CYN Unbound Analogue:_BR_957 Unbound Unbound
1d7wB Unbound Unbound Analogue:CYN Unbound Analogue:_BR_957 Unbound Unbound
1dnuA Unbound Unbound Analogue:SCN_5 Unbound Unbound Unbound Unbound
1dnuB Unbound Unbound Analogue:SCN_4 Unbound Unbound Unbound Unbound
1dnwA Unbound Unbound Analogue:CYN_3 Unbound Unbound Unbound Unbound
1dnwB Unbound Unbound Analogue:CYN_4 Unbound Unbound Unbound Unbound
1mhlA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1mhlB Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1mypA Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1mypB Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1cxpC Bound:HEM Bound:_CA Unbound Unbound Unbound Unbound Unbound
1cxpD Bound:HEM Bound:_CA Unbound Unbound Unbound Unbound Unbound
1d2vC Bound:HEM Bound:_CA Unbound Unbound Unbound Unbound Unbound
1d2vD Bound:HEM Bound:_CA Unbound Unbound Unbound Unbound Unbound
1d5lC Bound:HEM Bound:_CA Unbound Unbound Unbound Unbound Unbound
1d5lD Bound:HEM Bound:_CA Unbound Unbound Unbound Unbound Unbound
1d7wC Bound:HEM Bound:_CA Unbound Unbound Unbound Unbound Unbound
1d7wD Bound:HEM Bound:_CA Unbound Unbound Unbound Unbound Unbound
1dnuC Bound:HEM Bound:_CA Unbound Unbound Unbound Unbound Unbound
1dnuD Bound:HEM Bound:_CA Unbound Unbound Unbound Unbound Unbound
1dnwC Bound:HEM Bound:_CA Unbound Unbound Unbound Unbound Unbound
1dnwD Bound:HEM Bound:_CA Unbound Unbound Unbound Unbound Unbound
1mhlC Bound:HEM Bound:_CA Unbound Unbound Unbound Unbound Unbound
1mhlD Bound:HEM Bound:_CA Unbound Unbound Unbound Unbound Unbound
1mypC Bound:HEM Bound:_CA Unbound Unbound Unbound Unbound Unbound
1mypD Bound:HEM Bound:_CA Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P05164 & literature [5], [10], [11]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1cxpA GLN 91;HIS 95 ASP 94(Heme);ASP 96(Calcium)
1cxpB GLN 91;HIS 95 ASP 94(Heme);ASP 96(Calcium)
1d2vA GLN 91;HIS 95 ASP 94(Heme);ASP 96(Calcium)
1d2vB GLN 91;HIS 95 ASP 94(Heme);ASP 96(Calcium)
1d5lA GLN 91;HIS 95 ASP 94(Heme);ASP 96(Calcium)
1d5lB GLN 91;HIS 95 ASP 94(Heme);ASP 96(Calcium)
1d7wA GLN 91;HIS 95 ASP 94(Heme);ASP 96(Calcium)
1d7wB GLN 91;HIS 95 ASP 94(Heme);ASP 96(Calcium)
1dnuA GLN 91;HIS 95 ASP 94(Heme);ASP 96(Calcium)
1dnuB GLN 91;HIS 95 ASP 94(Heme);ASP 96(Calcium)
1dnwA GLN 91;HIS 95 ASP 94(Heme);ASP 96(Calcium)
1dnwB GLN 91;HIS 95 ASP 94(Heme);ASP 96(Calcium)
1mhlA GLN 91;HIS 95 ASP 94(Heme);ASP 96(Calcium)
1mhlB GLN 91;HIS 95 ASP 94(Heme);ASP 96(Calcium)
1mypA GLN 91;HIS 95 ASP 94(Heme);ASP 96(Calcium)
1mypB GLN 91;HIS 95 ASP 94(Heme);ASP 96(Calcium)
1cxpC ARG 239 GLU 242;MET 243(Heme);HIS 336(Heme iron);THR 168;PHE 170;ASP 172;SER 174(Calcium) CSO 150(Cysteine sulfenic acid)
1cxpD ARG 239 GLU 242;MET 243(Heme);HIS 336(Heme iron);THR 168;PHE 170;ASP 172;SER 174(Calcium) CSO 150(Cysteine sulfenic acid)
1d2vC ARG 239 GLU 242;MET 243(Heme);HIS 336(Heme iron);THR 168;PHE 170;ASP 172;SER 174(Calcium) CSO 150(Cysteine sulfenic acid)
1d2vD ARG 239 GLU 242;MET 243(Heme);HIS 336(Heme iron);THR 168;PHE 170;ASP 172;SER 174(Calcium) CSO 150(Cysteine sulfenic acid)
1d5lC ARG 239 GLU 242;MET 243(Heme);HIS 336(Heme iron);THR 168;PHE 170;ASP 172;SER 174(Calcium) CSO 150(Cysteine sulfenic acid)
1d5lD ARG 239 GLU 242;MET 243(Heme);HIS 336(Heme iron);THR 168;PHE 170;ASP 172;SER 174(Calcium) CSO 150(Cysteine sulfenic acid)
1d7wC ARG 239 GLU 242;MET 243(Heme);HIS 336(Heme iron);THR 168;PHE 170;ASP 172;SER 174(Calcium) CSO 150(Cysteine sulfenic acid)
1d7wD ARG 239 GLU 242;MET 243(Heme);HIS 336(Heme iron);THR 168;PHE 170;ASP 172;SER 174(Calcium) CSO 150(Cysteine sulfenic acid)
1dnuC ARG 239 GLU 242;MET 243(Heme);HIS 336(Heme iron);THR 168;PHE 170;ASP 172;SER 174(Calcium) CSO 150(Cysteine sulfenic acid)
1dnuD ARG 239 GLU 242;MET 243(Heme);HIS 336(Heme iron);THR 168;PHE 170;ASP 172;SER 174(Calcium) CSO 150(Cysteine sulfenic acid)
1dnwC ARG 239 GLU 242;MET 243(Heme);HIS 336(Heme iron);THR 168;PHE 170;ASP 172;SER 174(Calcium) CSO 150(Cysteine sulfenic acid)
1dnwD ARG 239 GLU 242;MET 243(Heme);HIS 336(Heme iron);THR 168;PHE 170;ASP 172;SER 174(Calcium) CSO 150(Cysteine sulfenic acid)
1mhlC ARG 239 GLU 242;MET 243(Heme);HIS 336(Heme iron);THR 168;PHE 170;ASP 172;SER 174(Calcium) CYS 150(Cysteine sulfenic acid)
1mhlD ARG 239 GLU 242;MET 243(Heme);HIS 336(Heme iron);THR 168;PHE 170;ASP 172;SER 174(Calcium) CYS 150(Cysteine sulfenic acid)
1mypC ARG 239 GLU 242;MET 243(Heme);HIS 336(Heme iron);THR 168;PHE 170;ASP 172;SER 174(Calcium) CYS 150(Cysteine sulfenic acid)
1mypD ARG 239 GLU 242;MET 243(Heme);HIS 336(Heme iron);THR 168;PHE 170;ASP 172;SER 174(Calcium) CYS 150(Cysteine sulfenic acid)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[5]
[6]
[10]
Fig.3
[11]
p.10970-10973
[12]
SCHEME IV, p.5004
[17]
Scheme 1, p.1178
[18]
p.11964
[22]

References
[1]
Resource
Comments
Medline ID
PubMed ID 2824790
Journal J Mol Biol
Year 1987
Volume 196
Pages 919-25
Authors Fenna RE
Title Crystallization and subunit structure of canine myeloperoxidase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 2832613
Journal J Mol Biol
Year 1988
Volume 199
Pages 395-6
Authors Sutton BJ, Little C, Olsen RL, Willassen NP
Title Preliminary crystallographic analysis of human myeloperoxidase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 2559209
Journal J Mol Biol
Year 1989
Volume 210
Pages 681-3
Authors Zeng J, Fenna RE
Title Tetragonal crystals of canine myeloperoxidase suitable for X-ray structural analysis.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 1321726
Journal FEBS Lett
Year 1992
Volume 302
Pages 189-91
Authors Jacquet A, Deleersnyder V, Garcia-Quintana L, Bollen A, Moguilevsky N
Title Site-directed mutants of human myeloperoxidase. A topological approach to the heme-binding site.
Related PDB
Related UniProtKB
[5]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 1320128
Journal J Mol Biol
Year 1992
Volume 226
Pages 185-207
Authors Zeng J, Fenna RE
Title X-ray crystal structure of canine myeloperoxidase at 3 A resolution.
Related PDB 1myp
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 8037771
Journal Biochem Biophys Res Commun
Year 1994
Volume 202
Pages 73-81
Authors Jacquet A, Garcia-Quintana L, Deleersnyder V, Fenna R, Bollen A, Moguilevsky N
Title Site-directed mutagenesis of human myeloperoxidase: further identification of residues involved in catalytic activity and heme interaction.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 8062820
Journal EMBO J
Year 1994
Volume 13
Pages 3438-47
Authors Nelson RE, Fessler LI, Takagi Y, Blumberg B, Keene DR, Olson PF, Parker CG, Fessler JH
Title Peroxidasin: a novel enzyme-matrix protein of Drosophila development.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 8020506
Journal Eur J Biochem
Year 1994
Volume 222
Pages 677-85
Authors Floris R, Kim Y, Babcock GT, Wever R
Title Optical spectrum of myeloperoxidase. Origin of the red shift.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 8132563
Journal J Biol Chem
Year 1994
Volume 269
Pages 8388-92
Authors Hori H, Fenna RE, Kimura S, Ikeda-Saito M
Title Aromatic substrate molecules bind at the distal heme pocket of myeloperoxidase.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 167-744
Medline ID 95142692
PubMed ID 7840679
Journal Arch Biochem Biophys
Year 1995
Volume 316
Pages 653-6
Authors Fenna R, Zeng J, Davey C
Title Structure of the green heme in myeloperoxidase.
Related PDB 1mhl
Related UniProtKB P05164
[11]
Resource
Comments
Medline ID
PubMed ID 8718890
Journal Biochemistry
Year 1996
Volume 35
Pages 10967-73
Authors Davey CA, Fenna RE
Title 2.3 A resolution X-ray crystal structure of the bisubstrate analogue inhibitor salicylhydroxamic acid bound to human myeloperoxidase: a model for a prereaction complex with hydrogen peroxide.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 9478947
Journal J Biol Chem
Year 1998
Volume 273
Pages 4997-5005
Authors Hazen SL, d'Avignon A, Anderson MM, Hsu FF, Heinecke JW
Title Human neutrophils employ the myeloperoxidase-hydrogen peroxide-chloride system to oxidize alpha-amino acids to a family of reactive aldehydes. Mechanistic studies identifying labile intermediates along the reaction pathway.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 10395733
Journal Arch Biochem Biophys
Year 1999
Volume 367
Pages 173-84
Authors Nomura K, Hoshino K, Suzuki N
Title The primary and higher order structures of sea urchin ovoperoxidase as determined by cDNA cloning and predicted by homology modeling.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 10585414
Journal J Biol Chem
Year 1999
Volume 274
Pages 35441-8
Authors Lardinois OM, Medzihradszky KF, Ortiz de Montellano PR
Title Spin trapping and protein cross-linking of the lactoperoxidase protein radical.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 10069970
Journal J Exp Biol
Year 1999
Volume 202
Pages 809-16
Authors Ribeiro JM, Valenzuela JG
Title Purification and cloning of the salivary peroxidase/catechol oxidase of the mosquito Anopheles albimanus.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 10805914
Journal Biopolymers
Year 2000
Volume 57
Pages 169-78
Authors Araki K, Takeuchi H
Title Effects of pH and chloride concentration on resonance Raman spectra of human myeloperoxidase and Raman microspectroscopic analysis of enzyme state in azurophilic granules.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 11087440
Journal Chem Res Toxicol
Year 2000
Volume 13
Pages 1174-80
Authors Stansbury KH, Noll DM, Groopman JD, Trush MA
Title Enzyme-mediated dialdehyde formation: an alternative pathway for benzo[a]pyrene 7,8-dihydrodiol bioactivation.
Related PDB
Related UniProtKB
[18]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 167-744
Medline ID 20229799
PubMed ID 10766826
Journal J Biol Chem
Year 2000
Volume 275
Pages 11964-71
Authors Fiedler TJ, Davey CA, Fenna RE
Title X-ray crystal structure and characterization of halide-binding sites of human myeloperoxidase at 1.8 A resolution.
Related PDB 1cxp 1d2v
Related UniProtKB P05164
[19]
Resource
Comments
Medline ID
PubMed ID 10994874
Journal Redox Rep
Year 2000
Volume 5
Pages 197-206
Authors Nauseef WM, McCormick S, Goedken M
Title Impact of missense mutations on biosynthesis of myeloperoxidase.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 11159195
Journal Am J Pathol
Year 2001
Volume 158
Pages 581-92
Authors Yang JJ, Preston GA, Pendergraft WF, Segelmark M, Heeringa P, Hogan SL, Jennette JC, Falk RJ
Title Internalization of proteinase 3 is concomitant with endothelial cell apoptosis and internalization of myeloperoxidase with generation of intracellular oxidants.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 11237766
Journal Biochem Biophys Res Commun
Year 2001
Volume 281
Pages 1024-9
Authors Shin K, Hayasawa H, Lonnerdal B
Title Mutations affecting the calcium-binding site of myeloperoxidase and lactoperoxidase.
Related PDB
Related UniProtKB
[22]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 167-744
Medline ID 21562373
PubMed ID 11705390
Journal Biochemistry
Year 2001
Volume 40
Pages 13990-7
Authors Blair-Johnson M, Fiedler T, Fenna R
Title Human myeloperoxidase: structure of a cyanide complex and its interaction with bromide and thiocyanate substrates at 1.9 A resolution.
Related PDB 1d5l 1d7w 1dnu 1dnw
Related UniProtKB P05164
[23]
Resource
Comments
Medline ID
PubMed ID 11513872
Journal FEBS Lett
Year 2001
Volume 503
Pages 147-50
Authors Furtmuller PG, Jantschko W, Regelsberger G, Jakopitsch C, Moguilevsky N, Obinger C
Title A transient kinetic study on the reactivity of recombinant unprocessed monomeric myeloperoxidase.
Related PDB
Related UniProtKB

Comments
This enzyme is composed of light chain (chain A or B in PDB) and heavy chain (chain C or D in PDB).
Although this enzyme binds a calcium ion, it is not directly involved in catalysis.

Created Updated
2005-04-04 2009-02-26