PMID- 22913772
OWN - NLM
STAT- MEDLINE
DCOM- 20121119
LR  - 20211021
IS  - 1520-4995 (Electronic)
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 51
IP  - 37
DP  - 2012 Sep 18
TI  - Reactive cysteine in the structural Zn(2+) site of the C1B domain from PKCalpha.
PG  - 7263-77
LID - 10.1021/bi300750w [doi]
AB  - Structural cysteine-rich Zn(2+) sites that stabilize protein folds are considered 
      to be unreactive. In this article, we identified a reactive cysteine residue, 
      Cys151, in a treble-clef zinc finger with a Cys(3)His coordination sphere. The 
      protein in question is the C1B domain of Protein Kinase Calpha (PKCalpha). Mass-tagging 
      cysteine assays of several C1B variants were employed to ascertain the site 
      specificity of the covalent modification. The reactivity of Cys151 in C1B also 
      manifests itself in the structural dynamics of the Zn(2+) coordination sphere 
      where the Sgamma of Cys151 alternates between the Zn(2+)-bound thiolate and free 
      thiol states. We used NMR-detected pH titrations, ZZ-exchange spectroscopy, and 
      residual dipolar coupling (RDC)-driven structure refinement to characterize the 
      two exchanging conformations of C1B that differ in zinc coordination. Our data 
      suggest that Cys151 serves as an entry point for the reactive oxygen species that 
      activate PKCalpha in a process involving Zn(2+) release.
FAU - Stewart, Mikaela D
AU  - Stewart MD
AD  - Department of Biochemistry and Biophysics, Texas A&M University, College Station, 
      Texas 77843-2128, United States.
FAU - Igumenova, Tatyana I
AU  - Igumenova TI
LA  - eng
GR  - T32 GM065088/GM/NIGMS NIH HHS/United States
GR  - 5-T32GM065088/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120905
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.13 (Prkca protein, mouse)
RN  - EC 2.7.11.13 (Protein Kinase C-alpha)
RN  - J41CSQ7QDS (Zinc)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Cysteine/*chemistry/metabolism
MH  - Mice
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - Protein Kinase C-alpha/*chemistry/metabolism
MH  - Protein Structure, Tertiary
MH  - Reactive Oxygen Species/*chemistry/metabolism
MH  - Zinc/*chemistry/metabolism
MH  - Zinc Fingers
PMC - PMC3645944
MID - NIHMS405744
EDAT- 2012/08/24 06:00
MHDA- 2012/12/10 06:00
PMCR- 2013/09/18
CRDT- 2012/08/24 06:00
PHST- 2012/08/24 06:00 [entrez]
PHST- 2012/08/24 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2013/09/18 00:00 [pmc-release]
AID - 10.1021/bi300750w [doi]
PST - ppublish
SO  - Biochemistry. 2012 Sep 18;51(37):7263-77. doi: 10.1021/bi300750w. Epub 2012 Sep 
      5.