PMID- 10656833
OWN - NLM
STAT- MEDLINE
DCOM- 20000314
LR  - 20131121
IS  - 0022-2836 (Print)
IS  - 0022-2836 (Linking)
VI  - 296
IP  - 1
DP  - 2000 Feb 11
TI  - Active and inhibited human catalase structures: ligand and NADPH binding and
      catalytic mechanism.
PG  - 295-309
AB  - 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.
CI  - Copyright 2000 Academic Press.
FAU - Putnam, C D
AU  - Putnam CD
AD  - Department of Molecular Biology, Skaggs Institute for Chemical Biology, The
      Scripps Research Institute, MB 4, 10550 North Torrey Pines Road, La Jolla, CA
      92037, USA.
FAU - Arvai, A S
AU  - Arvai AS
FAU - Bourne, Y
AU  - Bourne Y
FAU - Tainer, J A
AU  - Tainer JA
LA  - eng
SI  - PDB/1DGB
SI  - PDB/1DGF
SI  - PDB/1DGG
SI  - PDB/1DGH
GR  - GM39345/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (Cyanides)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (tyrosyl radical Y(D))
RN  - 059QF0KO0R (Water)
RN  - 42HK56048U (Tyrosine)
RN  - 42VZT0U6YR (Heme)
RN  - 53-59-8 (NADP)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.11.1.6 (Catalase)
RN  - ZF80H5GXUF (Amitrole)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amitrole/chemistry/metabolism
MH  - Binding Sites
MH  - Catalase/antagonists & inhibitors/*chemistry/*metabolism
MH  - Catalysis
MH  - Crystallization
MH  - Crystallography, X-Ray
MH  - Cyanides/chemistry/metabolism
MH  - Electrons
MH  - Enzyme Inhibitors/chemistry/*metabolism
MH  - Heme/metabolism
MH  - Humans
MH  - Hydrogen Bonding
MH  - Hydrogen Peroxide/metabolism
MH  - Models, Chemical
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - NADP/chemistry/*metabolism
MH  - Protein Conformation
MH  - Substrate Specificity
MH  - Tyrosine/analogs & derivatives/chemistry/metabolism
MH  - Water/metabolism
EDAT- 2000/02/05 09:00
MHDA- 2000/03/18 09:00
CRDT- 2000/02/05 09:00
PHST- 2000/02/05 09:00 [pubmed]
PHST- 2000/03/18 09:00 [medline]
PHST- 2000/02/05 09:00 [entrez]
AID - 10.1006/jmbi.1999.3458 [doi]
AID - S0022-2836(99)93458-7 [pii]
PST - ppublish
SO  - J Mol Biol. 2000 Feb 11;296(1):295-309. doi: 10.1006/jmbi.1999.3458.