PMID- 22928870
OWN - NLM
STAT- MEDLINE
DCOM- 20130225
LR  - 20131121
IS  - 1520-5207 (Electronic)
IS  - 1520-5207 (Linking)
VI  - 116
IP  - 40
DP  - 2012 Oct 11
TI  - The role of the distal histidine in H2O2 activation and heme protection in both 
      peroxidase and globin functions.
PG  - 12065-77
LID - 10.1021/jp300014b [doi]
AB  - The distal histidine mutations of dehaloperoxidase-hemoglobin A (DHP A) to 
      aspartate (H55D) and asparagine (H55N) have been prepared to study the role 
      played by the distal histidine in both activation and protection against 
      oxidation by radicals in heme proteins. The H55D and H55N mutants of DHP A have 
      ~6-fold and ~11-fold lower peroxidase activities than wild type enzyme toward the 
      oxidation of 2,4,6-trichlorophenol (TCP) to yield 2,6-dichloroquinone (DCQ) in 
      the presence of H(2)O(2). The origin of the lower rate constants may be the 
      solvent-exposed conformations of distal D55 and N55, which would have the dual 
      effect of destabilizing the binding of H(2)O(2) to the heme iron, and of removing 
      the acid-base catalyst necessary for the heterolytic O-O bond cleavage of 
      heme-bound H(2)O(2) (i.e., compound 0). The partial peroxidase activity of H55D 
      can be explained if one considers that there are two conformations of the distal 
      aspartate (open and closed) by analogy with the distal histidine. We hypothesize 
      that the distal aspartate has an active conformation in the distal pocket 
      (closed). Although the open form is observed in the low-temperature X-ray crystal 
      structure of ferric H55D, the closed form is observed in the FTIR spectrum of the 
      carbonmonoxy form of the H55D mutant. Consistent with this model, the H55D mutant 
      also shows inhibition of TCP oxidation by 4-bromophenol (4-BP). Consistent with 
      the protection hypothesis, compound ES, the tyrosyl radical-containing ferryl 
      intermediate observed in WT DHP A, was not observed in H55D.
FAU - Zhao, Junjie
AU  - Zhao J
AD  - Department of Chemistry, North Carolina State University, Raleigh, North Carolina 
      27695, USA.
FAU - de Serrano, Vesna
AU  - de Serrano V
FAU - Dumarieh, Rania
AU  - Dumarieh R
FAU - Thompson, Matt
AU  - Thompson M
FAU - Ghiladi, Reza A
AU  - Ghiladi RA
FAU - Franzen, Stefan
AU  - Franzen S
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20120927
PL  - United States
TA  - J Phys Chem B
JT  - The journal of physical chemistry. B
JID - 101157530
RN  - 0 (Chlorophenols)
RN  - 0 (Quinones)
RN  - 42VZT0U6YR (Heme)
RN  - 4QD397987E (Histidine)
RN  - 9034-51-9 (Hemoglobin A)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.11.1.- (Peroxidases)
RN  - MHS8C5BAUZ (2,4,6-trichlorophenol)
SB  - IM
MH  - Biocatalysis
MH  - Chlorophenols/chemistry/metabolism
MH  - Heme/chemistry/*metabolism
MH  - Hemoglobin A/chemistry/*metabolism
MH  - Histidine/chemistry/genetics/*metabolism
MH  - Hydrogen Peroxide/chemistry/*metabolism
MH  - Models, Molecular
MH  - Molecular Structure
MH  - Mutation
MH  - Oxidation-Reduction
MH  - Peroxidases/chemistry/*metabolism
MH  - Quinones/chemistry/metabolism
EDAT- 2012/08/30 06:00
MHDA- 2013/02/26 06:00
CRDT- 2012/08/30 06:00
PHST- 2012/08/30 06:00 [entrez]
PHST- 2012/08/30 06:00 [pubmed]
PHST- 2013/02/26 06:00 [medline]
AID - 10.1021/jp300014b [doi]
PST - ppublish
SO  - J Phys Chem B. 2012 Oct 11;116(40):12065-77. doi: 10.1021/jp300014b. Epub 2012 
      Sep 27.