PDBsum entry: 1dgg

Oxidoreductase

PDB id: 1dgg

Contents

Protein chains

497 a.a. *

Ligands

CYN-HEM ×4

NDP ×2

Waters ×1493

* Residue conservation analysis

PDB id:

1dgg

Name:

Oxidoreductase

Title:

Human erythrocyte catalse cyanide complex

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:

1.80Å R-factor: 0.178 R-free: 0.221

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: 17-Feb-00

Protein chains

P04040  (CATA_HUMAN) -  Catalase

Seq: 527 a.a.

Struc: 497 a.a.

Enzyme reactions

• Enzyme class: E.C.1.11.1.6 - Catalase.
• Reaction: 2 H₂O₂ = O₂ + 2 H₂O
• Cofactor: Heme; Manganese

Heme (Bound ligand (Het Group name = HEM) matches with 95.00% similarity) Manganese

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: plasma membrane (10 terms)
• Biological process: cellular response to growth factor stimulus (24 terms)
• Biochemical function: oxidoreductase activity (9 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.