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PDBsum entry 2cpo

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protein ligands metals links
Oxidoreductase PDB id
2cpo
Jmol
Contents
Protein chain
299 a.a. *
Ligands
NAG
NAG-NAG ×2
MAN ×8
HEM
Metals
_MN
Waters ×172
* Residue conservation analysis
PDB id:
2cpo
Name: Oxidoreductase
Title: Chloroperoxidase
Structure: Chloroperoxidase. Chain: a. Synonym: cpo, clp. Ec: 1.11.1.10
Source: Leptoxyphium fumago. Organism_taxid: 5474. Atcc: 16373
Resolution:
2.10Å     R-factor:   0.186     R-free:   0.228
Authors: M.Sundaramoorthy,T.L.Poulos
Key ref:
M.Sundaramoorthy et al. (1995). The crystal structure of chloroperoxidase: a heme peroxidase--cytochrome P450 functional hybrid. Structure, 3, 1367-1377. PubMed id: 8747463 DOI: 10.1016/S0969-2126(01)00274-X
Date:
10-Feb-96     Release date:   12-Feb-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P04963  (PRXC_CALFU) -  Chloroperoxidase
Seq:
Struc:
373 a.a.
299 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.1.11.1.10  - Chloride peroxidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RH + Cl- + H2O2 = RCl + 2 H2O
RH
+ Cl(-)
+ H(2)O(2)
= RCl
+ 2 × H(2)O
      Cofactor: Heme
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!
  Biochemical function     peroxidase activity     1 term  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(01)00274-X Structure 3:1367-1377 (1995)
PubMed id: 8747463  
 
 
The crystal structure of chloroperoxidase: a heme peroxidase--cytochrome P450 functional hybrid.
M.Sundaramoorthy, J.Terner, T.L.Poulos.
 
  ABSTRACT  
 
BACKGROUND: Chloroperoxidase (CPO) is a versatile heme-containing enzyme that exhibits peroxidase, catalase and cytochrome P450-like activities in addition to catalyzing halogenation reactions. The structure determination of CPO was undertaken to help elucidate those structural features that enable the enzyme to exhibit these multiple activities. RESULTS: Despite functional similarities with other heme enzymes, CPO folds into a novel tertiary structure dominated by eight helical segments. The catalytic base, required to cleave the peroxide O-O bond, is glutamic acid rather than histidine as in other peroxidases. CPO contains a hydrophobic patch above the heme that could be the binding site for substrates that undergo P450-like reactions. The crystal structure also shows extensive glycosylation with both N- and O-linked glycosyl chains. CONCLUSIONS: The proximal side of the heme in CPO resembles cytochrome P450 because a cysteine residue serves as an axial heme ligand, whereas the distal side of the heme is 'peroxidase-like' in that polar residues form the peroxide-binding site. Access to the heme pocket is restricted to the distal face such that small organic substrates can interact with the iron-linked oxygen atom which accounts for the P450-like reactions catalyzed by chloroperoxidase.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. . (a) Stereo representation of the CPO molecule. α helices are shown in red and are labeled with upper-case letters from A–H and 3[10] helices are labeled with primed letters. The β pair is shown as blue arrows. The cation is indicated as a pink sphere near a heme propionate. The N and C termini are only 5.6 å apart and are bridged by a solvent molecule (not shown). (b) Stereo diagram of the Cα trace of CPO with every tenth Cα position labeled. (Figure made with SETOR [52].). Figure 2. . (a) Stereo representation of the CPO molecule. α helices are shown in red and are labeled with upper-case letters from A–H and 3[10] helices are labeled with primed letters. The β pair is shown as blue arrows. The cation is indicated as a pink sphere near a heme propionate. The N and C termini are only 5.6 å apart and are bridged by a solvent molecule (not shown). (b) Stereo diagram of the Cα trace of CPO with every tenth Cα position labeled. (Figure made with SETOR [[4]52].).
Figure 8.
Figure 8. . (a) F[o]–F[c] omit electron-density maps contoured at 2.5σ for the 14 carbohydrate attachment sites found in the P2[1]2[1]2[1] crystal form. (b) The structure of the most extensively branched site which is attached to Asn93. Figure 8. . (a) F[o]–F[c] omit electron-density maps contoured at 2.5σ for the 14 carbohydrate attachment sites found in the P2[1]2[1]2[1] crystal form. (b) The structure of the most extensively branched site which is attached to Asn93.
 
  The above figures are reprinted by permission from Cell Press: Structure (1995, 3, 1367-1377) copyright 1995.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21308129 O.Shoji, and Y.Watanabe (2011).
Design of H2O2-dependent oxidation catalyzed by hemoproteins.
  Metallomics, 3, 379-388.  
20498847 K.M.Manoj, A.Baburaj, B.Ephraim, F.Pappachan, P.P.Maviliparambathu, U.K.Vijayan, S.V.Narayanan, K.Periasamy, E.A.George, and L.T.Mathew (2010).
Explaining the atypical reaction profiles of heme enzymes with a novel mechanistic hypothesis and kinetic treatment.
  PLoS One, 5, e10601.  
20544970 L.J.Smith, A.Kahraman, and J.M.Thornton (2010).
Heme proteins--diversity in structural characteristics, function, and folding.
  Proteins, 78, 2349-2368.  
20495915 M.Hofrichter, R.Ullrich, M.J.Pecyna, C.Liers, and T.Lundell (2010).
New and classic families of secreted fungal heme peroxidases.
  Appl Microbiol Biotechnol, 87, 871-897.  
20697922 O.Shoji, T.Fujishiro, S.Nagano, S.Tanaka, T.Hirose, Y.Shiro, and Y.Watanabe (2010).
Understanding substrate misrecognition of hydrogen peroxide dependent cytochrome P450 from Bacillus subtilis.
  J Biol Inorg Chem, 15, 1331-1339.
PDB codes: 2zqj 2zqx
19769330 P.R.Ortiz de Montellano (2010).
Hydrocarbon hydroxylation by cytochrome P450 enzymes.
  Chem Rev, 110, 932-948.  
19675645 A.Butler, and M.Sandy (2009).
Mechanistic considerations of halogenating enzymes.
  Nature, 460, 848-854.  
19434406 M.J.Pecyna, R.Ullrich, B.Bittner, A.Clemens, K.Scheibner, R.Schubert, and M.Hofrichter (2009).
Molecular characterization of aromatic peroxygenase from Agrocybe aegerita.
  Appl Microbiol Biotechnol, 84, 885-897.  
18291314 C.S.Neumann, D.G.Fujimori, and C.T.Walsh (2008).
Halogenation strategies in natural product biosynthesis.
  Chem Biol, 15, 99.  
18407660 F.Gruia, D.Ionascu, M.Kubo, X.Ye, J.Dawson, R.L.Osborne, S.G.Sligar, I.Denisov, A.Das, T.L.Poulos, J.Terner, and P.M.Champion (2008).
Low-frequency dynamics of Caldariomyces fumago chloroperoxidase probed by femtosecond coherence spectroscopy.
  Biochemistry, 47, 5156-5167.  
18625069 O.Bader, Y.Krauke, and B.Hube (2008).
Processing of predicted substrates of fungal Kex2 proteinases from Candida albicans, C. glabrata, Saccharomyces cerevisiae and Pichia pastoris.
  BMC Microbiol, 8, 116.  
17077084 H.M.Girvan, H.E.Seward, H.S.Toogood, M.R.Cheesman, D.Leys, and A.W.Munro (2007).
Structural and spectroscopic characterization of P450 BM3 mutants with unprecedented P450 heme iron ligand sets. New heme ligation states influence conformational equilibria in P450 BM3.
  J Biol Chem, 282, 564-572.
PDB codes: 2ij2 2ij3 2ij4
17511866 J.Z.Liu, and M.Wang (2007).
Improvement of activity and stability of chloroperoxidase by chemical modification.
  BMC Biotechnol, 7, 23.  
17487972 L.Zhi, Y.Jiang, Y.Wang, M.Hu, S.Li, and Y.Ma (2007).
Effects of additives on the thermostability of chloroperoxidase.
  Biotechnol Prog, 23, 729-733.  
17928290 Y.Sugano, R.Muramatsu, A.Ichiyanagi, T.Sato, and M.Shoda (2007).
DyP, a unique dye-decolorizing peroxidase, represents a novel heme peroxidase family: ASP171 replaces the distal histidine of classical peroxidases.
  J Biol Chem, 282, 36652-36658.  
16880954 J.L.Anderson, and S.K.Chapman (2006).
Molecular mechanisms of enzyme-catalysed halogenation.
  Mol Biosyst, 2, 350-357.  
16790441 K.Kühnel, W.Blankenfeldt, J.Terner, and I.Schlichting (2006).
Crystal structures of chloroperoxidase with its bound substrates and complexed with formate, acetate, and nitrate.
  J Biol Chem, 281, 23990-23998.
PDB codes: 2civ 2ciw 2cix 2ciy 2ciz 2cj0 2cj1 2cj2
16314410 L.De Smet, S.N.Savvides, E.Van Horen, G.Pettigrew, and J.J.Van Beeumen (2006).
Structural and mutagenesis studies on the cytochrome c peroxidase from Rhodobacter capsulatus provide new insights into structure-function relationships of bacterial di-heme peroxidases.
  J Biol Chem, 281, 4371-4379.
PDB code: 1zzh
16628447 M.Hofrichter, and R.Ullrich (2006).
Heme-thiolate haloperoxidases: versatile biocatalysts with biotechnological and environmental significance.
  Appl Microbiol Biotechnol, 71, 276-288.  
16774243 R.Zhang, N.Nagraj, D.S.Lansakara-P, L.P.Hager, and M.Newcomb (2006).
Kinetics of two-electron oxidations by the compound I derivative of chloroperoxidase, a model for cytochrome P450 oxidants.
  Org Lett, 8, 2731-2734.  
15066989 D.Li, D.J.Stuehr, S.R.Yeh, and D.L.Rousseau (2004).
Heme distortion modulated by ligand-protein interactions in inducible nitric-oxide synthase.
  J Biol Chem, 279, 26489-26499.  
15062772 I.Matsunaga, and Y.Shiro (2004).
Peroxide-utilizing biocatalysts: structural and functional diversity of heme-containing enzymes.
  Curr Opin Chem Biol, 8, 127-132.  
14763829 N.Spreti, R.Germani, A.Incani, and G.Savelli (2004).
Stabilization of chloroperoxidase by polyethylene glycols in aqueous media: kinetic studies and synthetic applications.
  Biotechnol Prog, 20, 96.  
12519760 D.S.Lee, A.Yamada, H.Sugimoto, I.Matsunaga, H.Ogura, K.Ichihara, S.Adachi, S.Y.Park, and Y.Shiro (2003).
Substrate recognition and molecular mechanism of fatty acid hydroxylation by cytochrome P450 from Bacillus subtilis. Crystallographic, spectroscopic, and mutational studies.
  J Biol Chem, 278, 9761-9767.
PDB code: 1izo
12637529 E.Pinakoulaki, U.Pfitzner, B.Ludwig, and C.Varotsis (2003).
Direct detection of Fe(IV)[double bond]O intermediates in the cytochrome aa3 oxidase from Paracoccus denitrificans/H2O2 reaction.
  J Biol Chem, 278, 18761-18766.  
12655056 J.T.Groves (2003).
The bioinorganic chemistry of iron in oxygenases and supramolecular assemblies.
  Proc Natl Acad Sci U S A, 100, 3569-3574.  
12488315 X.Wang, H.Tachikawa, X.Yi, K.M.Manoj, and L.P.Hager (2003).
Two-dimensional NMR study of the heme active site structure of chloroperoxidase.
  J Biol Chem, 278, 7765-7774.  
12576477 X.Yi, A.Conesa, P.J.Punt, and L.P.Hager (2003).
Examining the role of glutamic acid 183 in chloroperoxidase catalysis.
  J Biol Chem, 278, 13855-13859.  
12351824 K.Meno, S.Jennings, A.T.Smith, A.Henriksen, and M.Gajhede (2002).
Structural analysis of the two horseradish peroxidase catalytic residue variants H42E and R38S/H42E: implications for the catalytic cycle.
  Acta Crystallogr D Biol Crystallogr, 58, 1803-1812.
PDB codes: 1kzm 4atj
11121105 A.Celik, P.M.Cullis, M.J.Sutcliffe, R.Sangar, and E.L.Raven (2001).
Engineering the active site of ascorbate peroxidase.
  Eur J Biochem, 268, 78-85.  
11168405 E.Baciocchi, M.Fabbrini, O.Lanzalunga, L.Manduchi, and G.Pochetti (2001).
Prochiral selectivity in H(2)O(2)-promoted oxidation of arylalkanols catalysed by chloroperoxidase. The role of the interactions between the OH group and the amino-acid residues in the enzyme active site.
  Eur J Biochem, 268, 665-672.  
11168358 S.Yoshioka, S.Takahashi, H.Hori, K.Ishimori, and I.Morishima (2001).
Proximal cysteine residue is essential for the enzymatic activities of cytochrome P450cam.
  Eur J Biochem, 268, 252-259.  
10652281 A.Tuynman, J.L.Spelberg, I.M.Kooter, H.E.Schoemaker, and R.Wever (2000).
Enantioselective epoxidation and carbon-carbon bond cleavage catalyzed by Coprinus cinereus peroxidase and myeloperoxidase.
  J Biol Chem, 275, 3025-3030.  
11102789 F.van Rantwijk, and R.A.Sheldon (2000).
Selective oxygen transfer catalysed by heme peroxidases: synthetic and mechanistic aspects.
  Curr Opin Biotechnol, 11, 554-564.  
10652305 M.Couture, D.J.Stuehr, and D.L.Rousseau (2000).
The ferrous dioxygen complex of the oxygenase domain of neuronal nitric-oxide synthase.
  J Biol Chem, 275, 3201-3205.  
10828985 T.Uchida, T.Mogi, and T.Kitagawa (2000).
Resonance raman studies of oxo intermediates in the reaction of pulsed cytochrome bo with hydrogen peroxide.
  Biochemistry, 39, 6669-6678.  
10052937 D.Shelver, M.V.Thorsteinsson, R.L.Kerby, S.Y.Chung, G.P.Roberts, M.F.Reynolds, R.B.Parks, and J.N.Burstyn (1999).
Identification of two important heme site residues (cysteine 75 and histidine 77) in CooA, the CO-sensing transcription factor of Rhodospirillum rubrum.
  Biochemistry, 38, 2669-2678.  
10021409 J.Littlechild (1999).
Haloperoxidases and their role in biotransformation reactions.
  Curr Opin Chem Biol, 3, 28-34.  
10480900 S.Adak, C.Crooks, Q.Wang, B.R.Crane, J.A.Tainer, E.D.Getzoff, and D.J.Stuehr (1999).
Tryptophan 409 controls the activity of neuronal nitric-oxide synthase by regulating nitric oxide feedback inhibition.
  J Biol Chem, 274, 26907-26911.  
10535936 X.Yi, M.Mroczko, K.M.Manoj, X.Wang, and L.P.Hager (1999).
Replacement of the proximal heme thiolate ligand in chloroperoxidase with a histidine residue.
  Proc Natl Acad Sci U S A, 96, 12412-12417.  
9667928 A.T.Smith, and N.C.Veitch (1998).
Substrate binding and catalysis in heme peroxidases.
  Curr Opin Chem Biol, 2, 269-278.  
9751642 M.Sundaramoorthy, J.Terner, and T.L.Poulos (1998).
Stereochemistry of the chloroperoxidase active site: crystallographic and molecular-modeling studies.
  Chem Biol, 5, 461-473.  
9551547 T.L.Poulos, C.S.Raman, and H.Li (1998).
NO news is good news.
  Structure, 6, 255-258.  
9115415 B.K.Yeung, X.Wang, J.A.Sigman, P.A.Petillo, and Y.Lu (1997).
Construction and characterization of a manganese-binding site in cytochrome c peroxidase: towards a novel manganese peroxidase.
  Chem Biol, 4, 215-221.  
9334294 B.R.Crane, A.S.Arvai, R.Gachhui, C.Wu, D.K.Ghosh, E.D.Getzoff, D.J.Stuehr, and J.A.Tainer (1997).
The structure of nitric oxide synthase oxygenase domain and inhibitor complexes.
  Science, 278, 425-431.
PDB codes: 1noc 1nos 2nos
9261177 L.M.Landino, B.C.Crews, J.K.Gierse, S.D.Hauser, and L.J.Marnett (1997).
Mutational analysis of the role of the distal histidine and glutamine residues of prostaglandin-endoperoxide synthase-2 in peroxidase catalysis, hydroperoxide reduction, and cyclooxygenase activation.
  J Biol Chem, 272, 21565-21574.  
9047320 M.P.Roach, Y.P.Chen, S.A.Woodin, D.E.Lincoln, C.R.Lovell, and J.H.Dawson (1997).
Notomastus lobatus chloroperoxidase and Amphitrite ornata dehaloperoxidase both contain histidine as their proximal heme iron ligand.
  Biochemistry, 36, 2197-2202.  
9245421 M.Tanaka, K.Ishimori, M.Mukai, T.Kitagawa, and I.Morishima (1997).
Catalytic activities and structural properties of horseradish peroxidase distal His42 --> Glu or Gln mutant.
  Biochemistry, 36, 9889-9898.  
8955082 A.L.Tsai, V.Berka, P.F.Chen, and G.Palmer (1996).
Characterization of endothelial nitric-oxide synthase and its reaction with ligand by electron paramagnetic resonance spectroscopy.
  J Biol Chem, 271, 32563-32571.  
8917498 P.G.Debrunner, A.F.Dexter, C.E.Schulz, Y.M.Xia, and L.P.Hager (1996).
Mössbauer and electron paramagnetic resonance studies of chloroperoxidase following mechanism-based inactivation with allylbenzene.
  Proc Natl Acad Sci U S A, 93, 12791-12798.  
8931549 S.A.Martinis, S.R.Blanke, L.P.Hager, S.G.Sligar, G.H.Hoa, J.J.Rux, and J.H.Dawson (1996).
Probing the heme iron coordination structure of pressure-induced cytochrome P420cam.
  Biochemistry, 35, 14530-14536.  
8931550 S.R.Blanke, S.A.Martinis, S.G.Sligar, L.P.Hager, J.J.Rux, and J.H.Dawson (1996).
Probing the heme iron coordination structure of alkaline chloroperoxidase.
  Biochemistry, 35, 14537-14543.  
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.