PDBsum entry 1opm

Go to PDB code: 
protein ligands metals links
Oxidoreductase PDB id
Protein chain
310 a.a. *
IYG ×2
GOL ×5
_CU ×2
Waters ×151
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Oxidized (cu2+) peptidylglycine alpha-hydroxylating monooxyg (phm) with bound substrate
Structure: Protein (peptidylglycine alpha-hydroxylating monooxygenase). Chain: a. Synonym: peptidylglycine monooxygenase, peptidylglycine 2- hydroxylase, phm. Engineered: yes. Other_details: oxidized (cu2+), substrate bound
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Cell_line: dg44. Organ: ovary. Organelle: secretory vesicles. Cellular_location: excreted. Expressed in: cricetulus griseus. Expression_system_taxid: 10029.
2.10Å     R-factor:   0.200     R-free:   0.259
Authors: S.T.Prigge,L.M.Amzel
Key ref:
S.T.Prigge et al. (1999). Substrate-mediated electron transfer in peptidylglycine alpha-hydroxylating monooxygenase. Nat Struct Biol, 6, 976-983. PubMed id: 10504734 DOI: 10.1038/13351
25-May-99     Release date:   29-Sep-99    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P14925  (AMD_RAT) -  Peptidyl-glycine alpha-amidating monooxygenase
976 a.a.
310 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.  - Peptidylglycine monooxygenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Peptidylglycine + ascorbate + O2 = peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
Bound ligand (Het Group name = GOL)
matches with 50.00% similarity
+ O(2)
Bound ligand (Het Group name = IYG)
matches with 40.00% similarity
+ dehydroascorbate
+ H(2)O
      Cofactor: Cu cation
   Enzyme class 2: E.C.  - Peptidylamidoglycolate lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Peptidylamidoglycolate = peptidyl amide + glyoxylate
Bound ligand (Het Group name = IYG)
matches with 40.00% similarity
= peptidyl amide
Bound ligand (Het Group name = GOL)
matches with 57.14% similarity
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     oxidation-reduction process   2 terms 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1038/13351 Nat Struct Biol 6:976-983 (1999)
PubMed id: 10504734  
Substrate-mediated electron transfer in peptidylglycine alpha-hydroxylating monooxygenase.
S.T.Prigge, A.S.Kolhekar, B.A.Eipper, R.E.Mains, L.M.Amzel.
Peptide amidation is a ubiquitous posttranslational modification of bioactive peptides. Peptidylglycine alpha-hydroxylating monooxygenase (PHM; EC, the enzyme that catalyzes the first step of this reaction, is composed of two domains, each of which binds one copper atom. The coppers are held 11 A apart on either side of a solvent-filled interdomain cleft, and the PHM reaction requires electron transfer between these sites. A plausible mechanism for electron transfer might involve interdomain motion to decrease the distance between the copper atoms. Our experiments show that PHM catalytic core (PHMcc) is enzymatically active in the crystal phase, where interdomain motion is not possible. Instead, structures of two states relevant to catalysis indicate that water, substrate and active site residues may provide an electron transfer pathway that exists only during the PHM catalytic cycle.
  Selected figure(s)  
Figure 5.
Figure 5. Stereo view of the electron density connecting Gln 170 and substrate in ox-PHMcc−sub. The 2F[o] - F[c] electron density (contoured at 1 ) is shown for the side chain of Gln 170, the substrate Ac-diI-YG and a bridging water molecule. Substrate and protein atoms are colored by atom type: iodine atoms are purple, and water molecules are represented by red spheres. Dotted lines indicate bonds to the two copper atoms (green spheres). This figure was made using the program SETOR^55.
Figure 6.
Figure 6. Superposition of reduced and oxidized PHMcc active sites. Active site copper ligands are shown in blue (reduced PHMcc) and yellow (oxidized PHMcc). Shown on the right are CuA and its ligands (His 107, His 108 and His 172); shown on the left are CuB and its ligands (His 242, His 244, Met 314 and one solvent atom). This figure was made using the program SETOR^55.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1999, 6, 976-983) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21298193 F.G.Mutti, M.Gullotti, L.Casella, L.Santagostini, R.Pagliarin, K.K.Andersson, M.F.Iozzi, and G.Zoppellaro (2011).
A new chiral, poly-imidazole N8-ligand and the related di- and tri-copper(II) complexes: synthesis, theoretical modelling, spectroscopic properties, and biomimetic stereoselective oxidations.
  Dalton Trans, 40, 5436-5457.  
20544364 C.R.Hess, J.P.Klinman, and N.J.Blackburn (2010).
The copper centers of tyramine β-monooxygenase and its catalytic-site methionine variants: an X-ray absorption study.
  J Biol Inorg Chem, 15, 1195-1207.  
20648645 D.Bousquet-Moore, R.E.Mains, and B.A.Eipper (2010).
Peptidylgycine alpha-amidating monooxygenase and copper: a gene-nutrient interaction critical to nervous system function.
  J Neurosci Res, 88, 2535-2545.  
20715282 E.Langella, S.Pierre, W.Ghattas, M.Giorgi, M.Réglier, M.Saviano, L.Esposito, and R.Hardré (2010).
Probing the peptidylglycine alpha-hydroxylating monooxygenase active site with novel 4-phenyl-3-butenoic acid based inhibitors.
  ChemMedChem, 5, 1568-1576.  
19695261 C.C.Su, F.Yang, F.Long, D.Reyon, M.D.Routh, D.W.Kuo, A.K.Mokhtari, J.D.Van Ornam, K.L.Rabe, J.A.Hoy, Y.J.Lee, K.R.Rajashankar, and E.W.Yu (2009).
Crystal structure of the membrane fusion protein CusB from Escherichia coli.
  J Mol Biol, 393, 342-355.
PDB codes: 3h94 3h9i 3h9t 3ooc 3opo 3ow7
19604476 E.E.Chufán, M.De, B.A.Eipper, R.E.Mains, and L.M.Amzel (2009).
Amidation of bioactive peptides: the structure of the lyase domain of the amidating enzyme.
  Structure, 17, 965-973.
PDB codes: 3fvz 3fw0
19569683 N.R.McIntyre, E.W.Lowe, and D.J.Merkler (2009).
Imino-oxy acetic acid dealkylation as evidence for an inner-sphere alcohol intermediate in the reaction catalyzed by peptidylglycine alpha-hydroxylating monooxygenase.
  J Am Chem Soc, 131, 10308-10319.  
  18818385 S.D.Sharma, G.Raghuraman, M.S.Lee, N.R.Prabhakar, and G.K.Kumar (2009).
Intermittent hypoxia activates peptidylglycine alpha-amidating monooxygenase in rat brain stem via reactive oxygen species-mediated proteolytic processing.
  J Appl Physiol, 106, 12-19.  
18830721 S.M.Berry, J.R.Mayers, and N.A.Zehm (2009).
Models of noncoupled dinuclear copper centers in azurin.
  J Biol Inorg Chem, 14, 143-149.  
18032384 C.R.Hess, M.M.McGuirl, and J.P.Klinman (2008).
Mechanism of the Insect Enzyme, Tyramine {beta}-Monooxygenase, Reveals Differences from the Mammalian Enzyme, Dopamine {beta}-Monooxygenase.
  J Biol Chem, 283, 3042-3049.  
18952446 D.J.Merkler, A.S.Asser, L.E.Baumgart, N.Carballo, S.E.Carpenter, G.H.Chew, C.C.Cosner, J.Dusi, L.C.Galloway, A.B.Lowe, E.W.Lowe, L.King, R.D.Kendig, P.C.Kline, R.Malka, K.A.Merkler, N.R.McIntyre, M.Romero, B.J.Wilcox, and T.C.Owen (2008).
Substituted hippurates and hippurate analogs as substrates and inhibitors of peptidylglycine alpha-hydroxylating monooxygenase (PHM).
  Bioorg Med Chem, 16, 10061-10074.  
17374503 J.M.Bollinger, and C.Krebs (2007).
Enzymatic C-H activation by metal-superoxo intermediates.
  Curr Opin Chem Biol, 11, 151-158.  
17562710 M.De, G.D.Ciccotosto, R.E.Mains, and B.A.Eipper (2007).
Trafficking of a secretory granule membrane protein is sensitive to copper.
  J Biol Chem, 282, 23362-23371.  
17011183 A.C.Rosenzweig, and M.H.Sazinsky (2006).
Structural insights into dioxygen-activating copper enzymes.
  Curr Opin Struct Biol, 16, 729-735.  
16330540 A.T.Bauman, E.T.Yukl, K.Alkevich, A.L.McCormack, and N.J.Blackburn (2006).
The hydrogen peroxide reactivity of peptidylglycine monooxygenase supports a Cu(II)-superoxo catalytic intermediate.
  J Biol Chem, 281, 4190-4198.  
16791643 la Lande, H.Gérard, V.Moliner, G.Izzet, O.Reinaud, and O.Parisel (2006).
Theoretical modelling of tripodal CuN3 and CuN4 cuprous complexes interacting with O2, CO or CH3CN.
  J Biol Inorg Chem, 11, 593-608.  
16344970 B.F.Gherman, D.E.Heppner, W.B.Tolman, and C.J.Cramer (2006).
Models for dioxygen activation by the CuB site of dopamine beta-monooxygenase and peptidylglycine alpha-hydroxylating monooxygenase.
  J Biol Inorg Chem, 11, 197-205.  
17019721 B.F.Gherman, W.B.Tolman, and C.J.Cramer (2006).
Characterization of the structure and reactivity of monocopper-oxygen complexes supported by beta-diketiminate and anilido-imine ligands.
  J Comput Chem, 27, 1950-1961.  
17033702 D.E.Heppner, B.F.Gherman, W.B.Tolman, and C.J.Cramer (2006).
Can an ancillary ligand lead to a thermodynamically stable end-on 1 : 1 Cu-O2 adduct supported by a beta-diketiminate ligand?
  Dalton Trans, (), 4773-4782.  
16301310 J.P.Klinman (2006).
The copper-enzyme family of dopamine beta-monooxygenase and peptidylglycine alpha-hydroxylating monooxygenase: resolving the chemical pathway for substrate hydroxylation.
  J Biol Chem, 281, 3013-3016.  
16787093 R.Sarangi, N.Aboelella, K.Fujisawa, W.B.Tolman, B.Hedman, K.O.Hodgson, and E.I.Solomon (2006).
X-ray absorption edge spectroscopy and computational studies on LCuO2 species: Superoxide-Cu(II) versus peroxide-Cu(III) bonding.
  J Am Chem Soc, 128, 8286-8296.  
15691328 A.Asada, H.Orii, K.Watanabe, and M.Tsubaki (2005).
Planarian peptidylglycine-hydroxylating monooxygenase, a neuropeptide processing enzyme, colocalizes with cytochrome b561 along the central nervous system.
  FEBS J, 272, 942-955.  
15811799 A.Decker, and E.I.Solomon (2005).
Dioxygen activation by copper, heme and non-heme iron enzymes: comparison of electronic structures and reactivities.
  Curr Opin Chem Biol, 9, 152-163.  
16234916 R.L.Lieberman, and A.C.Rosenzweig (2005).
The quest for the particulate methane monooxygenase active site.
  Dalton Trans, (), 3390-3396.  
16100265 X.Siebert, B.A.Eipper, R.E.Mains, S.T.Prigge, N.J.Blackburn, and L.M.Amzel (2005).
The catalytic copper of peptidylglycine alpha-hydroxylating monooxygenase also plays a critical structural role.
  Biophys J, 89, 3312-3319.
PDB codes: 1yi9 1yip 1yjk 1yjl
15340147 P.Chen, and E.I.Solomon (2004).
O2 activation by binuclear Cu sites: noncoupled versus exchange coupled reaction mechanisms.
  Proc Natl Acad Sci U S A, 101, 13105-13110.  
15597398 S.Dove (2004).
Picolinic acids as inhibitors of dopamine beta-monooxygenase: QSAR and putative binding site.
  Arch Pharm (Weinheim), 337, 645-653.  
15131304 S.T.Prigge, B.A.Eipper, R.E.Mains, and L.M.Amzel (2004).
Dioxygen binds end-on to mononuclear copper in a precatalytic enzyme complex.
  Science, 304, 864-867.
PDB code: 1sdw
12966104 J.P.Evans, K.Ahn, and J.P.Klinman (2003).
Evidence that dioxygen and substrate activation are tightly coupled in dopamine beta-monooxygenase. Implications for the reactive oxygen species.
  J Biol Chem, 278, 49691-49698.  
12529325 R.El Meskini, V.C.Culotta, R.E.Mains, and B.A.Eipper (2003).
Supplying copper to the cuproenzyme peptidylglycine alpha-amidating monooxygenase.
  J Biol Chem, 278, 12278-12284.  
11863465 D.E.Benson, A.E.Haddy, and H.W.Hellinga (2002).
Converting a maltose receptor into a nascent binuclear copper oxygenase by computational design.
  Biochemistry, 41, 3262-3269.  
12404359 E.I.Solomon, P.Chen, M.Metz, S.K.Lee, and A.E.Palmer (2001).
Oxygen Binding, Activation, and Reduction to Water by Copper Proteins.
  Angew Chem Int Ed Engl, 40, 4570-4590.  
11330325 L.Que, and Y.Watanabe (2001).
Bioinorganic chemistry. Oxygenase pathways: oxo, peroxo, and superoxo.
  Science, 292, 651-653.  
11389601 S.Jaron, and N.J.Blackburn (2001).
Characterization of a half-apo derivative of peptidylglycine monooxygenase. Insight into the reactivity of each active site copper.
  Biochemistry, 40, 6867-6875.  
10891082 W.J.Driscoll, S.König, H.M.Fales, L.K.Pannell, B.A.Eipper, and G.P.Mueller (2000).
Peptidylglycine-alpha-hydroxylating monooxygenase generates two hydroxylated products from its mechanism-based suicide substrate, 4-phenyl-3-butenoic acid.
  Biochemistry, 39, 8007-8016.  
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.