PMID- 10334867
OWN - NLM
STAT- MEDLINE
DCOM- 19990624
LR  - 20131121
IS  - 0003-9861 (Print)
IS  - 0003-9861 (Linking)
VI  - 366
IP  - 1
DP  - 1999 Jun 1
TI  - Tyrosine modifications and inactivation of active site manganese superoxide
      dismutase mutant (Y34F) by peroxynitrite.
PG  - 82-8
AB  - Recent studies from this laboratory have demonstrated that human manganese
      superoxide dismutase (MnSOD) is a target for tyrosine nitration in several
      chronic inflammatory diseases including chronic organ rejection, arthritis, and
      tumorigenesis. Furthermore, we demonstrated that peroxynitrite (ONOO-) is the
      only known biological oxidant competent to inactivate enzymatic activity, nitrate
      critical tyrosine residues, and induce dityrosine formation in MnSOD. To
      elucidate the differential contributions of tyrosine nitration and oxidation
      during enzymatic inactivation, we now compare ONOO- treatment of native
      recombinant human MnSOD (WT-MnSOD) and a mutant, Y34F-MnSOD, in which tyrosine 34
      (the residue most susceptible to ONOO--mediated nitration) was mutated to
      phenylalanine. Both WT-MnSOD (IC50 = 65 microM, 15 microM MnSOD) and Y34F-MnSOD
      (IC50 = 55 microM, 15 microM Y34F) displayed similar dose-dependent sensitivity
      to ONOO--mediated inactivation. Compared to WT-MnSOD, the Y34F-MnSOD mutant
      demonstrated significantly less efficient tyrosine nitration and enhanced
      formation of dityrosine following treatment with ONOO-. Collectively, these
      results suggest that complete inactivation of MnSOD by ONOO- can occur
      independent of the active site tyrosine residue and includes not only nitration
      of critical tyrosine residues but also tyrosine oxidation and subsequent
      formation of dityrosine.
CI  - Copyright 1999 Academic Press.
FAU - MacMillan-Crow, L A
AU  - MacMillan-Crow LA
AD  - Departments of Surgery and Biochemistry/Molecular Genetics, University of Alabama
      at Birmingham, Birmingham, Alabama, 35294, USA. lmcrow@ccc.uab.edu
FAU - Thompson, J A
AU  - Thompson JA
LA  - eng
GR  - DK51629/DK/NIDDK NIH HHS/United States
GR  - HL45990/HL/NHLBI 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  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (Nitrates)
RN  - 0 (Recombinant Proteins)
RN  - 26404-66-0 (peroxynitric acid)
RN  - 42HK56048U (Tyrosine)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - *Catalytic Domain
MH  - Humans
MH  - Mutation
MH  - Nitrates/*pharmacology
MH  - Recombinant Proteins/antagonists & inhibitors
MH  - Superoxide Dismutase/*antagonists & inhibitors/genetics
MH  - *Tyrosine
EDAT- 1999/05/21 00:00
MHDA- 1999/05/21 00:01
CRDT- 1999/05/21 00:00
PHST- 1999/05/21 00:00 [pubmed]
PHST- 1999/05/21 00:01 [medline]
PHST- 1999/05/21 00:00 [entrez]
AID - S0003-9861(99)91202-X [pii]
AID - 10.1006/abbi.1999.1202 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 1999 Jun 1;366(1):82-8. doi: 10.1006/abbi.1999.1202.