Linked Life Data

12653548

Source:http://linkedlifedata.com/resource/pubmed/id/12653548

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2003-3-25
pubmed:databankReference
pubmed:abstractText
Glutamate dehydrogenase (GDH) is found in all organisms and catalyzes the reversible oxidative deamination of L-glutamate to 2-oxoglutarate. Unlike GDH from bacteria, mammalian GDH exhibits negative cooperativity with respect to coenzyme, activation by ADP, and inhibition by GTP. Presented here are the structures of apo bovine GDH, bovine GDH complexed with ADP, and the R463A mutant form of human GDH (huGDH) that is insensitive to ADP activation. In the absence of active site ligands, the catalytic cleft is in the open conformation, and the hexamers form long polymers in the crystal cell with more interactions than found in the abortive complex crystals. This is consistent with the fact that ADP promotes aggregation in solution. ADP is shown to bind to the second, inhibitory, NADH site yet causes activation. The beta-phosphates of the bound ADP interact with R459 (R463 in huGDH) on the pivot helix. The structure of the ADP-resistant, R463A mutant of human GDH is identical to native GDH with the exception of the truncated side chain on the pivot helix. Together, these results strongly suggest that ADP activates by facilitating the opening of the catalytic cleft. From alignment of GDH from various sources, it is likely that the antenna evolved in the protista prior to the formation of purine regulatory sites. This suggests that there was some selective advantage of the antenna itself and that animals evolved new functions for GDH through the addition of allosteric regulation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3446-56
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12653548-Adenosine Diphosphate, pubmed-meshheading:12653548-Allosteric Regulation, pubmed-meshheading:12653548-Amino Acid Sequence, pubmed-meshheading:12653548-Amino Acid Substitution, pubmed-meshheading:12653548-Animals, pubmed-meshheading:12653548-Apoenzymes, pubmed-meshheading:12653548-Binding Sites, pubmed-meshheading:12653548-Cattle, pubmed-meshheading:12653548-Enzyme Activation, pubmed-meshheading:12653548-Evolution, Molecular, pubmed-meshheading:12653548-Glutamate Dehydrogenase, pubmed-meshheading:12653548-Humans, pubmed-meshheading:12653548-Macromolecular Substances, pubmed-meshheading:12653548-Models, Molecular, pubmed-meshheading:12653548-Molecular Sequence Data, pubmed-meshheading:12653548-NAD, pubmed-meshheading:12653548-Protein Conformation, pubmed-meshheading:12653548-Protein Structure, Tertiary, pubmed-meshheading:12653548-Protein Subunits, pubmed-meshheading:12653548-Recombinant Proteins, pubmed-meshheading:12653548-Sequence Homology, Amino Acid, pubmed-meshheading:12653548-Static Electricity
pubmed:year
2003
pubmed:articleTitle
Structural studies on ADP activation of mammalian glutamate dehydrogenase and the evolution of regulation.
pubmed:affiliation
Donald Danforth Plant Science Center, St. Louis, Missouri 63132, USA.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't