PMID- 10872755
OWN - NLM
STAT- MEDLINE
DCOM- 20001107
LR  - 20161124
IS  - 0145-5680 (Print)
IS  - 0145-5680 (Linking)
VI  - 46
IP  - 3
DP  - 2000 May
TI  - Metal-catalyzed oxidation of brain-derived neurotrophic factor (BDNF): 
      selectivity and conformational consequences of histidine modification.
PG  - 685-96
AB  - We have studied the metal-catalyzed oxidation (MCO) of brain-derived neurotrophic 
      factor (BDNF) with regard to target sites and potential conformational changes of 
      the protein. The exposure of BDNF to three different levels of 
      ascorbate/Cu(II)/O2 [20 microM Cu(II), 2 mM ascorbate (level 1); 20 microM 
      Cu(II), 4 mM ascorbate (level 2); 40 microM Cu(II), 4 mM ascorbate (level 3)], 
      chosen based on the extent of chemical modification of Met and His, respectively, 
      resulted in the exclusive oxidation of a buried Met residue, Met92, at level 1 
      but in the predominant oxidation of His at level 3. His modification had a 
      significant impact on the structure of BDNF, as quantified by CD and ANSA 
      fluorescence measurements, while Met oxidation had not, also assessed through 
      complementary oxidation of BDNF through hydrogen peroxide. Our ultimate objective 
      was the correlation of the surface exposure of an oxidized His residue in a 
      protein with potential effects on the conformational integrity of the oxidized 
      protein. In a series of three proteins, human growth hormone (hGH), human relaxin 
      (hR1x), and BDNF, we have now observed that His oxidation is paralleled by 
      significant conformational changes when the target His residue is more surface 
      exposed (hR1x, BDNF) while conformational consequences of His modification are 
      less significant when the target His residues are more buried in the interior of 
      the protein (hGH).
FAU - Jensen, J L
AU  - Jensen JL
AD  - Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66047, 
      USA.
FAU - Kuczera, K
AU  - Kuczera K
FAU - Roy, S
AU  - Roy S
FAU - Schoneich, C
AU  - Schoneich C
LA  - eng
GR  - 2 T32 GM08359-11/GM/NIGMS NIH HHS/United States
GR  - P01AG12993-02/AG/NIA 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  - France
TA  - Cell Mol Biol (Noisy-le-grand)
JT  - Cellular and molecular biology (Noisy-le-Grand, France)
JID - 9216789
RN  - 0 (Amino Acids)
RN  - 0 (Anilino Naphthalenesulfonates)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Solvents)
RN  - 368GB5141J (Sodium Dodecyl Sulfate)
RN  - 4QD397987E (Histidine)
RN  - 630I4V6051 (1-anilino-8-naphthalenesulfonate)
RN  - 789U1901C5 (Copper)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acids/analysis
MH  - Anilino Naphthalenesulfonates
MH  - Brain-Derived Neurotrophic Factor/chemistry/*metabolism
MH  - Catalysis
MH  - Circular Dichroism
MH  - Copper/*metabolism
MH  - Electrophoresis, Polyacrylamide Gel/methods
MH  - Fluorescent Dyes
MH  - Histidine/*metabolism
MH  - Humans
MH  - Mass Spectrometry/methods
MH  - Molecular Sequence Data
MH  - Oxidation-Reduction
MH  - Protein Conformation
MH  - Sodium Dodecyl Sulfate
MH  - Solubility
MH  - Solvents
MH  - Ultracentrifugation/methods
EDAT- 2000/06/29 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/06/29 11:00
PHST- 2000/06/29 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/06/29 11:00 [entrez]
PST - ppublish
SO  - Cell Mol Biol (Noisy-le-grand). 2000 May;46(3):685-96.