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PDBsum entry 1dgf

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1dgf
Jmol
Contents
Protein chain
497 a.a. *
Ligands
ACT ×4
HEM ×4
NDP ×2
Waters ×2299
* Residue conservation analysis
PDB id:
1dgf
Name: Oxidoreductase
Title: Human erythrocyte catalase
Structure: Catalase. Chain: a, b, c, d. Ec: 1.11.1.6
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell: erythrocyte
Biol. unit: Tetramer (from PQS)
Resolution:
1.50Å     R-factor:   0.172     R-free:   0.192
Authors: C.D.Putnam,A.S.Arvai,Y.Bourne,J.A.Tainer
Key ref:
C.D.Putnam et al. (2000). Active and inhibited human catalase structures: ligand and NADPH binding and catalytic mechanism. J Mol Biol, 296, 295-309. PubMed id: 10656833 DOI: 10.1006/jmbi.1999.3458
Date:
24-Nov-99     Release date:   11-Feb-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P04040  (CATA_HUMAN) -  Catalase
Seq:
Struc:
 
Seq:
Struc:
527 a.a.
497 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.11.1.6  - Catalase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 2 H2O2 = O2 + 2 H2O
2 × H(2)O(2)
= O(2)
+ 2 × H(2)O
      Cofactor: Heme; Mn(2+)
Heme
Bound ligand (Het Group name = HEM) matches with 95.00% similarity
Mn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   14 terms 
  Biological process     small molecule metabolic process   28 terms 
  Biochemical function     antioxidant activity     12 terms  

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.1999.3458 J Mol Biol 296:295-309 (2000)
PubMed id: 10656833  
 
 
Active and inhibited human catalase structures: ligand and NADPH binding and catalytic mechanism.
C.D.Putnam, A.S.Arvai, Y.Bourne, J.A.Tainer.
 
  ABSTRACT  
 
Human catalase is an heme-containing peroxisomal enzyme that breaks down hydrogen peroxide to water and oxygen; it is implicated in ethanol metabolism, inflammation, apoptosis, aging and cancer. The 1. 5 A resolution human enzyme structure, both with and without bound NADPH, establishes the conserved features of mammalian catalase fold and assembly, implicates Tyr370 as the tyrosine radical, suggests the structural basis for redox-sensitive binding of cognate mRNA via the catalase NADPH binding site, and identifies an unexpectedly substantial number of water-mediated domain contacts. A molecular ruler mechanism based on observed water positions in the 25 A-long channel resolves problems for selecting hydrogen peroxide. Control of water-mediated hydrogen bonds by this ruler selects for the longer hydrogen peroxide and explains the paradoxical effects of mutations that increase active site access but lower catalytic rate. The heme active site is tuned without compromising peroxide binding through a Tyr-Arg-His-Asp charge relay, arginine residue to heme carboxylate group hydrogen bonding, and aromatic stacking. Structures of the non-specific cyanide and specific 3-amino-1,2, 4-triazole inhibitor complexes of human catalase identify their modes of inhibition and help reveal the catalytic mechanism of catalase. Taken together, these resting state and inhibited human catalase structures support specific, structure-based mechanisms for the catalase substrate recognition, reaction and inhibition and provide a molecular basis for understanding ethanol intoxication and the likely effects of human polymorphisms.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Structure of human catalase. (a) Stereo view of an individual subunit of human catalase with the central b-barrel in yellow, surrounding helices in blue. The active site heme (red) is surrounded by the b-barrel, a-helices and loops with one open face that is buried upon tetramerization. The NADPH (dark green) is on the far side of the molecule in this view. (b) Stereo view of an arm-exchanged dimer with the yellow and blue subunit and a purple subunit related by an approximate 2-fold perpendicular to the page. The orientation is similar to (a). In this dimer, both hemes remain exposed on one face. (c) Stereo view of the catalase tetramer with the addition of a second arm-exchanged dimer (orange and green). Formation of the tetramer buries the heme active sites from solvent. The orientation of the tetramer is rotated by about 45° perpendicular to the page relative to (a) and (b).
Figure 5.
Figure 5. Proposed tyrosine radical. Stereo view of the position of the proposed tyrosine radical, Tyr370, relative to the heme active site. A hydrogen-bonding network between His362, Asp335, and Tyr370 may provide a shorter electron transfer pathway than the backbone pathway that extends from Tyr358 to Tyr370.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 296, 295-309) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21368144 I.von der Hocht, J.H.van Wonderen, F.Hilbers, H.Angerer, F.Macmillan, and H.Michel (2011).
Interconversions of P and F intermediates of cytochrome c oxidase from Paracoccus denitrificans.
  Proc Natl Acad Sci U S A, 108, 3964-3969.  
20716293 D.E.Heck, M.Shakarjian, H.D.Kim, J.D.Laskin, and A.M.Vetrano (2010).
Mechanisms of oxidant generation by catalase.
  Ann N Y Acad Sci, 1203, 120-125.  
20544970 L.J.Smith, A.Kahraman, and J.M.Thornton (2010).
Heme proteins--diversity in structural characteristics, function, and folding.
  Proteins, 78, 2349-2368.  
19063897 D.S.Shin, M.Didonato, D.P.Barondeau, G.L.Hura, C.Hitomi, J.A.Berglund, E.D.Getzoff, S.C.Cary, and J.A.Tainer (2009).
Superoxide dismutase from the eukaryotic thermophile Alvinella pompejana: structures, stability, mechanism, and insights into amyotrophic lateral sclerosis.
  J Mol Biol, 385, 1534-1555.
PDB codes: 3f7k 3f7l
19751821 J.A.Leopold, and J.Loscalzo (2009).
Oxidative risk for atherothrombotic cardiovascular disease.
  Free Radic Biol Med, 47, 1673-1706.  
19139099 J.Suarez, K.Ranguelova, A.A.Jarzecki, J.Manzerova, V.Krymov, X.Zhao, S.Yu, L.Metlitsky, G.J.Gerfen, and R.S.Magliozzo (2009).
An Oxyferrous Heme/Protein-based Radical Intermediate Is Catalytically Competent in the Catalase Reaction of Mycobacterium tuberculosis Catalase-Peroxidase (KatG).
  J Biol Chem, 284, 7017-7029.  
19827095 S.Pakhomova, B.Gao, W.E.Boeglin, A.R.Brash, and M.E.Newcomer (2009).
The structure and peroxidase activity of a 33-kDa catalase-related protein from Mycobacterium avium ssp. paratuberculosis.
  Protein Sci, 18, 2559-2568.
PDB codes: 3e4w 3e4y
19804819 T.Yata, M.Nishikawa, C.Nishizaki, M.Oku, H.Yurimoto, Y.Sakai, and Y.Takakura (2009).
Control of hypoxia-induced tumor cell adhesion by cytophilic human catalase.
  Free Radic Biol Med, 47, 1772-1778.  
18652800 B.Gao, W.E.Boeglin, and A.R.Brash (2008).
Role of the conserved distal heme asparagine of coral allene oxide synthase (Asn137) and human catalase (Asn148): mutations affect the rate but not the essential chemistry of the enzymatic transformations.
  Arch Biochem Biophys, 477, 285-290.  
18315617 J.M.Wood, N.C.Gibbons, B.Chavan, and K.U.Schallreuter (2008).
Computer simulation of heterogeneous single nucleotide polymorphisms in the catalase gene indicates structural changes in the enzyme active site, NADPH-binding and tetramerization domains: a genetic predisposition for an altered catalase in patients with vitiligo?
  Exp Dermatol, 17, 366-371.  
18457571 M.Bayliak, D.Gospodaryov, H.Semchyshyn, and V.Lushchak (2008).
Inhibition of catalase by aminotriazole in vivo results in reduction of glucose-6-phosphate dehydrogenase activity in Saccharomyces cerevisiae cells.
  Biochemistry (Mosc), 73, 420-426.  
18498226 M.Zamocky, P.G.Furtmüller, and C.Obinger (2008).
Evolution of catalases from bacteria to humans.
  Antioxid Redox Signal, 10, 1527-1548.  
18375516 N.Colloc'h, L.Gabison, G.Monard, M.Altarsha, M.Chiadmi, G.Marassio, J.Sopkova-de Oliveira Santos, M.El Hajji, B.Castro, J.H.Abraini, and T.Prangé (2008).
Oxygen pressurized X-ray crystallography: probing the dioxygen binding site in cofactorless urate oxidase and implications for its catalytic mechanism.
  Biophys J, 95, 2415-2422.
PDB codes: 2zka 2zkb 3cks 3cku
18163197 S.Do Amaral, and B.P.Espósito (2008).
Fluorimetric study of the pro-oxidant activity of EUK8 in the presence of hydrogen peroxide.
  Biometals, 21, 425-432.  
18426413 V.Maresca, E.Flori, S.Briganti, A.Mastrofrancesco, C.Fabbri, A.M.Mileo, M.G.Paggi, and M.Picardo (2008).
Correlation between melanogenic and catalase activity in in vitro human melanocytes: a synergic strategy against oxidative stress.
  Pigment Cell Melanoma Res, 21, 200-205.  
17242507 E.K.Riise, M.S.Lorentzen, R.Helland, A.O.Smalås, H.K.Leiros, and N.P.Willassen (2007).
The first structure of a cold-active catalase from Vibrio salmonicida at 1.96 A reveals structural aspects of cold adaptation.
  Acta Crystallogr D Biol Crystallogr, 63, 135-148.
PDB code: 2isa
17158050 H.N.Kirkman, and G.F.Gaetani (2007).
Mammalian catalase: a venerable enzyme with new mysteries.
  Trends Biochem Sci, 32, 44-50.  
17229211 J.C.Grigg, C.L.Vermeiren, D.E.Heinrichs, and M.E.Murphy (2007).
Haem recognition by a Staphylococcus aureus NEAT domain.
  Mol Microbiol, 63, 139-149.
PDB codes: 2ite 2itf
17174478 J.J.Perry, L.Fan, and J.A.Tainer (2007).
Developing master keys to brain pathology, cancer and aging from the structural biology of proteins controlling reactive oxygen species and DNA repair.
  Neuroscience, 145, 1280-1299.  
16298761 H.de Groot, O.Auferkamp, T.Bramey, K.de Groot, M.Kirsch, H.G.Korth, F.Petrat, and R.Sustmann (2006).
Non-oxygen-forming pathways of hydrogen peroxide degradation by bovine liver catalase at low hydrogen peroxide fluxes.
  Free Radic Res, 40, 67-74.  
17108904 N.C.Gibbons, J.M.Wood, H.Rokos, and K.U.Schallreuter (2006).
Computer simulation of native epidermal enzyme structures in the presence and absence of hydrogen peroxide (H2O2): potential and pitfalls.
  J Invest Dermatol, 126, 2576-2582.  
16927253 P.Inbar, C.Q.Li, S.A.Takayama, M.R.Bautista, and J.Yang (2006).
Oligo(ethylene glycol) derivatives of thioflavin T as inhibitors of protein-amyloid interactions.
  Chembiochem, 7, 1563-1566.  
16513636 T.Tosha, T.Uchida, A.R.Brash, and T.Kitagawa (2006).
On the relationship of coral allene oxide synthase to catalase. A single active site mutation that induces catalase activity in coral allene oxide synthase.
  J Biol Chem, 281, 12610-12617.  
16417235 V.Maresca, E.Flori, S.Briganti, E.Camera, M.Cario-André, A.Taïeb, and M.Picardo (2006).
UVA-induced modification of catalase charge properties in the epidermis is correlated with the skin phototype.
  J Invest Dermatol, 126, 182-190.  
16244360 C.Jakopitsch, E.Droghetti, F.Schmuckenschlager, P.G.Furtmüller, G.Smulevich, and C.Obinger (2005).
Role of the main access channel of catalase-peroxidase in catalysis.
  J Biol Chem, 280, 42411-42422.  
15596434 K.Kobayashi, S.Yoshioka, Y.Kato, Y.Asano, and S.Aono (2005).
Regulation of aldoxime dehydratase activity by redox-dependent change in the coordination structure of the aldoxime-heme complex.
  J Biol Chem, 280, 5486-5490.  
15625113 M.L.Oldham, A.R.Brash, and M.E.Newcomer (2005).
The structure of coral allene oxide synthase reveals a catalase adapted for metabolism of a fatty acid hydroperoxide.
  Proc Natl Acad Sci U S A, 102, 297-302.
PDB code: 1u5u
16309371 M.Vitai, S.Fátrai, P.Rass, M.Csordás, and I.Tarnai (2005).
Simple PCR heteroduplex, SSCP mutation screening methods for the detection of novel catalase mutations in Hungarian patients with type 2 diabetes mellitus.
  Clin Chem Lab Med, 43, 1346-1350.  
15670921 N.Soh, O.Sakawaki, K.Makihara, Y.Odo, T.Fukaminato, T.Kawai, M.Irie, and T.Imato (2005).
Design and development of a fluorescent probe for monitoring hydrogen peroxide using photoinduced electron transfer.
  Bioorg Med Chem, 13, 1131-1139.  
15894226 S.Tafazoli, and P.J.O'Brien (2005).
Peroxidases: a role in the metabolism and side effects of drugs.
  Drug Discov Today, 10, 617-625.  
15272159 K.O.Håkansson, M.Brugna, and L.Tasse (2004).
The three-dimensional structure of catalase from Enterococcus faecalis.
  Acta Crystallogr D Biol Crystallogr, 60, 1374-1380.
PDB code: 1si8
12777400 C.Cao, Y.Leng, and D.Kufe (2003).
Catalase activity is regulated by c-Abl and Arg in the oxidative stress response.
  J Biol Chem, 278, 29667-29675.  
12950161 C.Cao, Y.Leng, X.Liu, Y.Yi, P.Li, and D.Kufe (2003).
Catalase is regulated by ubiquitination and proteosomal degradation. Role of the c-Abl and Arg tyrosine kinases.
  Biochemistry, 42, 10348-10353.  
12730222 D.E.Heck, A.M.Vetrano, T.M.Mariano, and J.D.Laskin (2003).
UVB light stimulates production of reactive oxygen species: unexpected role for catalase.
  J Biol Chem, 278, 22432-22436.  
12779342 F.Wu, L.J.Katsir, M.Seavy, and B.J.Gaffney (2003).
Role of radical formation at tyrosine 193 in the allene oxide synthase domain of a lipoxygenase-AOS fusion protein from coral.
  Biochemistry, 42, 6871-6880.  
14646074 P.Andreoletti, A.Pernoud, G.Sainz, P.Gouet, and H.M.Jouve (2003).
Structural studies of Proteus mirabilis catalase in its ground state, oxidized state and in complex with formic acid.
  Acta Crystallogr D Biol Crystallogr, 59, 2163-2168.
PDB codes: 1mqf 1nm0
12486720 P.Andreoletti, G.Sainz, M.Jaquinod, J.Gagnon, and H.M.Jouve (2003).
High-resolution structure and biochemical properties of a recombinant Proteus mirabilis catalase depleted in iron.
  Proteins, 50, 261-271.
PDB codes: 1e93 1h6n
12892493 V.S.Thompson, K.D.Schaller, and W.A.Apel (2003).
Purification and characterization of a novel thermo-alkali-stable catalase from Thermus brockianus.
  Biotechnol Prog, 19, 1292-1299.  
12557185 X.Carpena, M.Soriano, M.G.Klotz, H.W.Duckworth, L.J.Donald, W.Melik-Adamyan, I.Fita, and P.C.Loewen (2003).
Structure of the Clade 1 catalase, CatF of Pseudomonas syringae, at 1.8 A resolution.
  Proteins, 50, 423-436.
PDB code: 1m7s
12454454 G.N.Murshudov, A.I.Grebenko, J.A.Brannigan, A.A.Antson, V.V.Barynin, G.G.Dodson, Z.Dauter, K.S.Wilson, and W.R.Melik-Adamyan (2002).
The structures of Micrococcus lysodeikticus catalase, its ferryl intermediate (compound II) and NADPH complex.
  Acta Crystallogr D Biol Crystallogr, 58, 1972-1982.
PDB codes: 1gwe 1gwf 1gwh
12399505 L.Frankenberg, M.Brugna, and L.Hederstedt (2002).
Enterococcus faecalis heme-dependent catalase.
  J Bacteriol, 184, 6351-6356.  
11593016 K.S.Aulak, M.Miyagi, L.Yan, K.A.West, D.Massillon, J.W.Crabb, and D.J.Stuehr (2001).
Proteomic method identifies proteins nitrated in vivo during inflammatory challenge.
  Proc Natl Acad Sci U S A, 98, 12056-12061.  
11134921 M.K.Safo, F.N.Musayev, S.H.Wu, D.J.Abraham, and T.P.Ko (2001).
Structure of tetragonal crystals of human erythrocyte catalase.
  Acta Crystallogr D Biol Crystallogr, 57, 1-7.
PDB code: 1f4j
11496149 N.G.Milton, N.P.Mayor, and J.Rawlinson (2001).
Identification of amyloid-beta binding sites using an antisense peptide approach.
  Neuroreport, 12, 2561-2566.  
11389723 T.B.Brück, R.J.Fielding, M.C.Symons, and P.J.Harvey (2001).
Mechanism of nitrite-stimulated catalysis by lactoperoxidase.
  Eur J Biochem, 268, 3214-3222.  
11455600 W.Melik-Adamyan, J.Bravo, X.Carpena, J.Switala, M.J.Maté, I.Fita, and P.C.Loewen (2001).
Substrate flow in catalases deduced from the crystal structures of active site variants of HPII from Escherichia coli.
  Proteins, 44, 270-281.
PDB codes: 1gg9 1gge 1ggf 1ggh 1ggj 1ggk
11468413 X.Carpena, R.Perez, W.F.Ochoa, N.Verdaguer, M.G.Klotz, J.Switala, W.Melik-Adamyan, I.Fita, and P.C.Loewen (2001).
Crystallization and preliminary X-ray analysis of clade I catalases from Pseudomonas syringae and Listeria seeligeri.
  Acta Crystallogr D Biol Crystallogr, 57, 1184-1186.  
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.