| Structural highlights
1dgh is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ,
| | NonStd Res: | |
| Related: | 1dgb, 1dgf, 1dgg |
| Activity: | Catalase, with EC number 1.11.1.6 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[CATA_HUMAN] Defects in CAT are the cause of acatalasemia (ACATLAS) [MIM:614097]. A metabolic disorder characterized by absence of catalase activity in red cells and is often associated with ulcerating oral lesions.[1]
Function
[CATA_HUMAN] Occurs in almost all aerobically respiring organisms and serves to protect cells from the toxic effects of hydrogen peroxide. Promotes growth of cells including T-cells, B-cells, myeloid leukemia cells, melanoma cells, mastocytoma cells and normal and transformed fibroblast cells.[2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Active and inhibited human catalase structures: ligand and NADPH binding and catalytic mechanism.,Putnam CD, Arvai AS, Bourne Y, Tainer JA J Mol Biol. 2000 Feb 11;296(1):295-309. PMID:10656833[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wen JK, Osumi T, Hashimoto T, Ogata M. Molecular analysis of human acatalasemia. Identification of a splicing mutation. J Mol Biol. 1990 Jan 20;211(2):383-93. PMID:2308162 doi:http://dx.doi.org/10.1016/0022-2836(90)90359-T
- ↑ Takeuchi A, Miyamoto T, Yamaji K, Masuho Y, Hayashi M, Hayashi H, Onozaki K. A human erythrocyte-derived growth-promoting factor with a wide target cell spectrum: identification as catalase. Cancer Res. 1995 Apr 1;55(7):1586-9. PMID:7882369
- ↑ Putnam CD, Arvai AS, Bourne Y, Tainer JA. Active and inhibited human catalase structures: ligand and NADPH binding and catalytic mechanism. J Mol Biol. 2000 Feb 11;296(1):295-309. PMID:10656833 doi:http://dx.doi.org/10.1006/jmbi.1999.3458
|
