PMID- 23351100
OWN - NLM
STAT- MEDLINE
DCOM- 20130415
LR  - 20211021
IS  - 1520-4995 (Electronic)
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 52
IP  - 8
DP  - 2013 Feb 26
TI  - A conserved amphipathic ligand binding region influences k-path-dependent 
      activity of cytochrome C oxidase.
PG  - 1385-96
LID - 10.1021/bi3014505 [doi]
AB  - A conserved, crystallographically defined bile acid binding site was originally 
      identified in the membrane domain of mammalian and bacterial cytochrome c oxidase 
      (CcO). Current studies show other amphipathic molecules including detergents, 
      fatty acids, steroids, and porphyrins bind to this site and affect the already 
      50% inhibited activity of the E101A mutant of Rhodobacter sphaeroides CcO as well 
      as altering the activity of wild-type and bovine enzymes. Dodecyl maltoside, 
      Triton X100, C12E8, lysophophatidylcholine, and CHOBIMALT detergents further 
      inhibit RsCcO E101A, with lesser inhibition observed in wild-type. The detergent 
      inhibition is overcome in the presence of micromolar concentrations of steroids 
      and porphyrin analogues including deoxycholate, cholesteryl hemisuccinate, 
      bilirubin, and protoporphyrin IX. In addition to alleviating detergent 
      inhibition, amphipathic carboxylates including arachidonic, docosahexanoic, and 
      phytanic acids stimulate the activity of E101A to wild-type levels by providing 
      the missing carboxyl group. Computational modeling of dodecyl maltoside, 
      bilirubin, and protoporphyrin IX into the conserved steroid site shows 
      energetically favorable binding modes for these ligands and suggests that a 
      groove at the interface of subunit I and II, including the entrance to the K-path 
      and helix VIII of subunit I, mediates the observed competitive ligand 
      interactions involving two overlapping sites. Spectral analysis indicates that 
      ligand binding to this region affects CcO activity by altering the 
      K-path-dependent electron transfer equilibrium between heme a and heme a(3). The 
      high affinity and specificity of a number of compounds for this region, and its 
      conservation and impact on CcO activity, support its physiological significance.
FAU - Hiser, Carrie
AU  - Hiser C
AD  - Department of Biochemistry and Molecular Biology, Michigan State University, East 
      Lansing, Michigan 48824, United States.
FAU - Buhrow, Leann
AU  - Buhrow L
FAU - Liu, Jian
AU  - Liu J
FAU - Kuhn, Leslie
AU  - Kuhn L
FAU - Ferguson-Miller, Shelagh
AU  - Ferguson-Miller S
LA  - eng
GR  - R01 GM026916/GM/NIGMS NIH HHS/United States
GR  - R37 GM026916/GM/NIGMS NIH HHS/United States
GR  - GM26916/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130212
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Bile Acids and Salts)
RN  - 0 (Detergents)
RN  - 0 (Protein Subunits)
RN  - 0 (Protoporphyrins)
RN  - 0 (dodecyl maltopyranoside)
RN  - 005990WHZZ (Deoxycholic Acid)
RN  - 69-79-4 (Maltose)
RN  - C2K325S808 (protoporphyrin IX)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - Bile Acids and Salts/metabolism
MH  - Bilirubin/metabolism
MH  - Binding Sites
MH  - Deoxycholic Acid/metabolism
MH  - Detergents/metabolism
MH  - Electron Transport Complex IV/*chemistry/genetics/*metabolism
MH  - Maltose/analogs & derivatives/metabolism
MH  - Molecular Docking Simulation
MH  - Point Mutation
MH  - Protein Binding
MH  - Protein Structure, Secondary
MH  - Protein Subunits/chemistry/genetics/metabolism
MH  - Protoporphyrins/metabolism
MH  - Rhodobacter sphaeroides/*enzymology/genetics/metabolism
MH  - Substrate Specificity
PMC - PMC3622084
MID - NIHMS445566
EDAT- 2013/01/29 06:00
MHDA- 2013/04/16 06:00
PMCR- 2014/02/26
CRDT- 2013/01/29 06:00
PHST- 2013/01/29 06:00 [entrez]
PHST- 2013/01/29 06:00 [pubmed]
PHST- 2013/04/16 06:00 [medline]
PHST- 2014/02/26 00:00 [pmc-release]
AID - 10.1021/bi3014505 [doi]
PST - ppublish
SO  - Biochemistry. 2013 Feb 26;52(8):1385-96. doi: 10.1021/bi3014505. Epub 2013 Feb 
      12.