PMID- 18361527
OWN - NLM
STAT- MEDLINE
DCOM- 20080623
LR  - 20201209
IS  - 1520-6106 (Print)
IS  - 1520-5207 (Linking)
VI  - 112
IP  - 15
DP  - 2008 Apr 17
TI  - Structure and dynamics of Cu(I) binding in copper chaperones Atox1 and CopZ: a 
      computer simulation study.
PG  - 4583-93
LID - 10.1021/jp711787x [doi]
AB  - Copper chaperones deliver reduced copper (i.e., Cu(I)) to metal-binding domains 
      of P-type ATPases in the cytoplasm of a range of organisms. Both chaperones and 
      target domains have a ferredoxin-like fold and metal-binding motifs involving two 
      Cys residues. Here, we investigated the Cu-binding geometry and structural 
      dynamics of two homologous Cu(I) chaperones, Homo sapiens Atox1 and Bacillus 
      subtilis CopZ, using a combination of quantum mechanical-molecular mechanics 
      (QM-MM) and classical molecular dynamics (MD) methods. Our QM-MM optimized 
      geometries for the holo- proteins suggested that Cu(I) in Atox1 favors a linear 
      Cys(S)-Cu-Cys(S) arrangement but that this angle is close to 150 degrees in CopZ. 
      Classical MD simulations suggest that both Atox1 and CopZ apo- forms have an 
      increased conformational flexibility as compared to the respective holo- forms. 
      This difference is most pronounced in CopZ and correlates with a lower in vitro 
      thermal stability. Both average fluctuation (i.e., rmsd) and radius of gyration 
      data demonstrate that the effects of Cu(I) coordination extend throughout the 
      proteins. Distinct deviations between the two homologues were found in 
      protein-solvent interactions, entropy of Cu(I) binding, and apo-protein Cys-Cys 
      distance distributions. Our in silico results provide new insights into copper 
      chaperone behavior with direct implications for copper transport mechanisms in 
      vivo.
FAU - Rodriguez-Granillo, Agustina
AU  - Rodriguez-Granillo A
AD  - Department of Biochemistry and Cell Biology, Rice University, 6100 Main Street, 
      Houston, Texas 77251, USA.
FAU - Wittung-Stafshede, Pernilla
AU  - Wittung-Stafshede P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080325
PL  - United States
TA  - J Phys Chem B
JT  - The journal of physical chemistry. B
JID - 101157530
RN  - 0 (ATOX1 protein, human)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Cation Transport Proteins)
RN  - 0 (CopZ protein, Enterococcus hirae)
RN  - 0 (Copper Transport Proteins)
RN  - 0 (Metallochaperones)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Trans-Activators)
RN  - 789U1901C5 (Copper)
SB  - IM
MH  - Bacterial Proteins/*chemistry
MH  - Binding Sites
MH  - Cation Transport Proteins/*chemistry
MH  - *Computer Simulation
MH  - Copper/*chemistry
MH  - Copper Transport Proteins
MH  - Humans
MH  - Magnetic Resonance Spectroscopy/methods
MH  - Metallochaperones
MH  - Models, Biological
MH  - Models, Molecular
MH  - Molecular Chaperones/*chemistry
MH  - Protein Structure, Tertiary
MH  - Quantum Theory
MH  - Thermodynamics
MH  - Time Factors
MH  - Trans-Activators/*chemistry
EDAT- 2008/03/26 09:00
MHDA- 2008/06/24 09:00
CRDT- 2008/03/26 09:00
PHST- 2008/03/26 09:00 [pubmed]
PHST- 2008/06/24 09:00 [medline]
PHST- 2008/03/26 09:00 [entrez]
AID - 10.1021/jp711787x [doi]
PST - ppublish
SO  - J Phys Chem B. 2008 Apr 17;112(15):4583-93. doi: 10.1021/jp711787x. Epub 2008 Mar 
      25.