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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
51
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pubmed:dateCreated |
2005-12-20
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pubmed:abstractText |
L-Serine inhibits the catalytic activity of Escherichia coli D-3-phosphoglycerate dehydrogenase (PGDH) by binding to its regulatory domain. This domain is a member of the ACT domain family of regulatory domains that are modulated by small molecules. A comparison of the phi and psi torsional angle differences between the crystal structures of PGDH solved in the presence and in the absence of L-serine demonstrated a clustering of significant angle deviations in the regulatory domain. A similar clustering was not observed in either of the other two structural domains of PGDH. In addition, significant differences were also observed at the active site and in the Trp-139 loop. To determine if these residues were functionally significant and not just due to other factors such as crystal packing, mutagenic analysis of these residues was performed. Not unexpectedly, this analysis showed that residues that affected the kcat/Km were grouped around the active site and those that affected the serine sensitivity were grouped in the regulatory domain. However, more significantly, residues that affected the cooperativity of inhibition of activity were identified at both locations. These latter residues represent structural elements that participate in both the initial and the ultimate events of the transfer of cooperative behavior from the regulatory domain to the active site. As such, their identification will assist in the elucidation of the pathway of cooperative interaction in this enzyme as well as in the elucidation of the regulatory mechanism of the ACT domain in general.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16363798-10222208,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16363798-10852732,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16363798-11278587,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16363798-11751050,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16363798-12511575,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16363798-12644455,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16363798-14718528,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16363798-15035616,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16363798-15451668,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16363798-15544321,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16363798-15823035,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16363798-7719856,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16363798-8662776,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16363798-9562556
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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 |
Dec
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pubmed:issn |
0006-2960
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
27
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
16844-52
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:16363798-Allosteric Regulation,
pubmed-meshheading:16363798-Allosteric Site,
pubmed-meshheading:16363798-Amino Acid Sequence,
pubmed-meshheading:16363798-Amino Acids,
pubmed-meshheading:16363798-Binding Sites,
pubmed-meshheading:16363798-Catalytic Domain,
pubmed-meshheading:16363798-Crystallography, X-Ray,
pubmed-meshheading:16363798-Enzyme Inhibitors,
pubmed-meshheading:16363798-Escherichia coli,
pubmed-meshheading:16363798-Hydrogen Bonding,
pubmed-meshheading:16363798-Kinetics,
pubmed-meshheading:16363798-Models, Molecular,
pubmed-meshheading:16363798-Mutagenesis, Site-Directed,
pubmed-meshheading:16363798-Mutation,
pubmed-meshheading:16363798-Phosphoglycerate Dehydrogenase,
pubmed-meshheading:16363798-Recombinant Proteins,
pubmed-meshheading:16363798-Serine
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pubmed:year |
2005
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pubmed:articleTitle |
Identification of amino acid residues contributing to the mechanism of cooperativity in Escherichia coli D-3-phosphoglycerate dehydrogenase.
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pubmed:affiliation |
Department of Molecular Biology & Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8103, St. Louis, Missouri 63110, USA. ggrant@wustl.edu
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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