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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-12-17
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pubmed:abstractText |
Progesterone triggers the resumption of meiosis in the amphibian oocyte through a signaling system at the plasma membrane. Analysis of [(3)H]ouabain and [(3)H]progesterone binding to the plasma membrane of the Rana pipiens oocyte indicates that progesterone competes with ouabain for a low affinity ouabain binding site on a 112kDa alpha1-subunit of the membrane Na/K-ATPase. Published amino acid sequences from both low and high affinity ouabain binding alpha1-subunits are compared, together with published site-directed mutagenesis studies of ouabain binding. We propose that the progesterone binding site is located in the external loop (23 amino acids) between the M1-M2 transmembrane helices. Analysis of loop topology and the countercurrent hydrophobicity/polarity gradients within the M1-M2 loop further suggest that the polar beta and hydrophobic alpha surfaces of the planar progesterone molecule interact with opposite sides of the amino acid loop. The 19-angular methyl group of progesterone is essential for activity; it could bind to the C-terminal region of the M1-M2 loop. Maximum biological activity requires formation of hydrogen-bond networks between the 3-keto group of progesterone and Arg(118), Asp(129) and possibly Glu(122-124) in the C-terminal region of the loop. The 20-keto group hydrogen may in turn hydrogen bond to Cys(111) near the M1 helix. Peptide flexibility undergoes a maximal transition near the midway point in the M1-M2 loop, suggesting that folding occurs within the loop, which further stabilizes progesterone binding.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-10323685,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-10426281,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-10864315,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-10877849,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-11016952,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-11136241,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-11152761,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-11212965,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-12027881,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-12084906,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-1377448,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-15541762,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-15641774,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-15890647,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-16014813,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-16165176,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-16880602,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-17219407,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-1851176,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-2537604,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-2539926,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-2544104,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-301217,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-302805,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-311639,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-313888,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-4843792,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-5788898,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-6087028,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-6981431,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-7108955,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-7929066,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-8016122,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-8415625,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-8631513,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-9027358,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-9050859,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-9125134,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-9346307,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-9620806,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17936318-9815123
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0039-128X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
73
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
27-40
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:17936318-Amino Acid Sequence,
pubmed-meshheading:17936318-Animals,
pubmed-meshheading:17936318-Binding Sites,
pubmed-meshheading:17936318-Cell Membrane,
pubmed-meshheading:17936318-Computer Simulation,
pubmed-meshheading:17936318-Crystallography, X-Ray,
pubmed-meshheading:17936318-Female,
pubmed-meshheading:17936318-Magnetic Resonance Spectroscopy,
pubmed-meshheading:17936318-Models, Biological,
pubmed-meshheading:17936318-Models, Molecular,
pubmed-meshheading:17936318-Molecular Sequence Data,
pubmed-meshheading:17936318-Molecular Structure,
pubmed-meshheading:17936318-Oocytes,
pubmed-meshheading:17936318-Ouabain,
pubmed-meshheading:17936318-Progesterone,
pubmed-meshheading:17936318-Protein Binding,
pubmed-meshheading:17936318-Rana pipiens,
pubmed-meshheading:17936318-Sequence Homology, Amino Acid,
pubmed-meshheading:17936318-Sodium-Potassium-Exchanging ATPase
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pubmed:year |
2008
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pubmed:articleTitle |
Progesterone binding to the alpha1-subunit of the Na/K-ATPase on the cell surface: insights from computational modeling.
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pubmed:affiliation |
Department of Physiology & Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USA. morrill@aecom.yu.edu
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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