Linked Life Data

15033488

Source:http://linkedlifedata.com/resource/pubmed/id/15033488

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-3-22
pubmed:abstractText
The production of circulating blood cells from bone marrow stem cells during hematopoiesis is accompanied by overall changes in gene expression which cause production of required functional proteins, such as hemoglobin in erythroid cells, as well as control of cell growth, preventing apoptosis of differentiating cells. Hematopoietic gene regulation is controlled by several specific transcription factors, including the factor Gata-1, which is required for erythrocyte maturation. Based on contacts observed in the NMR structure of the cGata-1 binding domain in complex with DNA, the protein's key DNA interface is interesting in being quite hydrophobic in nature, due to the presence of three leucine side chains protruding toward the DNA. Given the T-rich composition of the GATA DNA binding site, it is possible that thymine's unique 5-methyl group may mediate some of these hydrophobic contacts to increase the stability of binding. The hypothesis that thymine methyl groups are important to the free energy of binding between Gata and DNA is tested by measuring binding of an oligonucleotide substrate in which individual thymine bases are substituted with uracil. To test for any important base-pair specific interactions which may be hydrogen-bonded in character, we have also assayed Gata binding to oligonucleotides with base analogs which cannot make hydrogen bonds. We report that out of the binding site's five thymine methyl groups, only one appeared to make a notable contribution to binding affinity, with removal causing a loss of less than 1kcal/mol of binding free energy. On the other hand, perturbing the potential hydrogen-bonding surface of the DNAs major groove was found to cause a larger decrease in binding affinity than removal of any of the thymine methyl groups, with a loss of 2-3kcal/mol of binding free energy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
316
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
910-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15033488-Amino Acid Sequence, pubmed-meshheading:15033488-Animals, pubmed-meshheading:15033488-Apoptosis, pubmed-meshheading:15033488-Binding Sites, pubmed-meshheading:15033488-Chickens, pubmed-meshheading:15033488-DNA, pubmed-meshheading:15033488-DNA-Binding Proteins, pubmed-meshheading:15033488-Dose-Response Relationship, Drug, pubmed-meshheading:15033488-Erythroid-Specific DNA-Binding Factors, pubmed-meshheading:15033488-Hydrogen Bonding, pubmed-meshheading:15033488-Kinetics, pubmed-meshheading:15033488-Magnetic Resonance Spectroscopy, pubmed-meshheading:15033488-Models, Chemical, pubmed-meshheading:15033488-Models, Molecular, pubmed-meshheading:15033488-Molecular Sequence Data, pubmed-meshheading:15033488-Oligonucleotides, pubmed-meshheading:15033488-Protein Binding, pubmed-meshheading:15033488-Thermodynamics, pubmed-meshheading:15033488-Thymine, pubmed-meshheading:15033488-Transcription Factors, pubmed-meshheading:15033488-Ultraviolet Rays, pubmed-meshheading:15033488-Uracil, pubmed-meshheading:15033488-Zinc Fingers
pubmed:year
2004
pubmed:articleTitle
A molecular dissection of the interaction between the transcription factor Gata-1 zinc finger and DNA.
pubmed:affiliation
Department of Chemistry, Hope College, Holland, MI 49423, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.