Kinetic analysis of the role of histidine chloramines in hypochlorous acid mediated protein oxidation
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Kinetic analysis of the role of histidine chloramines in hypochlorous acid mediated protein oxidation. / Pattison, David I; Davies, Michael Jonathan.
In: Biochemistry, Vol. 44, No. 19, 17.05.2005, p. 7378-87.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Kinetic analysis of the role of histidine chloramines in hypochlorous acid mediated protein oxidation
AU - Pattison, David I
AU - Davies, Michael Jonathan
PY - 2005/5/17
Y1 - 2005/5/17
N2 - Hypochlorous acid (HOCl) is a powerful oxidant generated from H(2)O(2) and chloride ions by the heme enzyme myeloperoxidase (MPO) released from activated leukocytes. In addition to its potent antibacterial effects, excessive HOCl production can lead to host tissue damage, with this implicated in human diseases such as atherosclerosis, cystic fibrosis, and arthritis. HOCl reacts rapidly with biological materials, with proteins being major targets. Chlorinated amines (chloramines) formed from Lys and His side chains and alpha-amino groups on proteins are major products of these reactions; these materials are however also oxidants and can undergo further reactions. In this study, the kinetics of reaction of His side-chain chloramines with other protein components have been investigated by UV/visible spectroscopy and stopped flow methods at pH 7.4 and 22 degrees C, using the chloramines of the model compound 4-imidazoleacetic acid and N-alpha-acetyl-histidine. The second-order rate constants decrease in a similar order (Cys > Met > disulfide bonds > Trp approximately alpha-amino > Lys > Tyr > backbone amides > Arg) to the corresponding reactions of HOCl, but are typically 5-25 times slower. These rate constants are consistent with His side-chain chloramines being important secondary oxidants in HOCl-mediated damage. These studies suggest that formation and subsequent reactions of His side-chain chloramines may be responsible for the targeted secondary modification of selected protein residues by HOCl that has previously been observed experimentally and highlight the importance of chloramine structure on their subsequent reactivity.
AB - Hypochlorous acid (HOCl) is a powerful oxidant generated from H(2)O(2) and chloride ions by the heme enzyme myeloperoxidase (MPO) released from activated leukocytes. In addition to its potent antibacterial effects, excessive HOCl production can lead to host tissue damage, with this implicated in human diseases such as atherosclerosis, cystic fibrosis, and arthritis. HOCl reacts rapidly with biological materials, with proteins being major targets. Chlorinated amines (chloramines) formed from Lys and His side chains and alpha-amino groups on proteins are major products of these reactions; these materials are however also oxidants and can undergo further reactions. In this study, the kinetics of reaction of His side-chain chloramines with other protein components have been investigated by UV/visible spectroscopy and stopped flow methods at pH 7.4 and 22 degrees C, using the chloramines of the model compound 4-imidazoleacetic acid and N-alpha-acetyl-histidine. The second-order rate constants decrease in a similar order (Cys > Met > disulfide bonds > Trp approximately alpha-amino > Lys > Tyr > backbone amides > Arg) to the corresponding reactions of HOCl, but are typically 5-25 times slower. These rate constants are consistent with His side-chain chloramines being important secondary oxidants in HOCl-mediated damage. These studies suggest that formation and subsequent reactions of His side-chain chloramines may be responsible for the targeted secondary modification of selected protein residues by HOCl that has previously been observed experimentally and highlight the importance of chloramine structure on their subsequent reactivity.
KW - Amides
KW - Amines
KW - Aminocaproic Acid
KW - Arginine
KW - Chloramines
KW - Chromatography, High Pressure Liquid
KW - Glycine
KW - Histidine
KW - Hypochlorous Acid
KW - Imidazoles
KW - Kinetics
KW - Lysine
KW - Oligopeptides
KW - Oxidation-Reduction
KW - Protein Conformation
KW - Tyrosine
U2 - 10.1021/bi0474665
DO - 10.1021/bi0474665
M3 - Journal article
C2 - 15882077
VL - 44
SP - 7378
EP - 7387
JO - Biochemistry
JF - Biochemistry
SN - 0006-2960
IS - 19
ER -
ID: 129672025