Linked Life Data

15465043

Source:http://linkedlifedata.com/resource/pubmed/id/15465043

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-10-6
pubmed:databankReference
pubmed:abstractText
Dehydroquinate synthase (DHQS) is a potential target for the development of novel broad-spectrum antimicrobial drugs, active against both prokaryotes and lower eukaryotes. Structures have been reported for Aspergillus nidulans DHQS (AnDHQS) in complexes with a range of ligands. Analysis of these AnDHQS structures showed that a large-scale domain movement occurs during the normal catalytic cycle, with a complex series of structural elements propagating substrate binding-induced conformational changes away from the active site to distal locations. Compared to corresponding fungal enzymes, DHQS from bacterial species are both mono-functional and significantly smaller. We have therefore determined the structure of Staphylococcus aureus DHQS (SaDHQS) in five liganded states, allowing comparison of ligand-induced conformational changes and mechanisms of domain closure between fungal and bacterial enzymes. This comparative analysis shows that substrate binding initiates a large-scale domain closure in both species' DHQS and that the active site stereochemistry, of the catalytically competent closed-form enzyme thus produced, is also highly conserved. However, comparison of AnDHQS and SaDHQS open-form structures, and analysis of the putative dynamic processes by which the transition to the closed-form states are made, shows a far lower degree of similarity, indicating a significant structural divergence. As a result, both the nature of the propagation of conformational change and the mechanical systems involved in this propagation are quite different between the DHQSs from the two species.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
343
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
533-46
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15465043-Amino Acid Sequence, pubmed-meshheading:15465043-Aspergillus nidulans, pubmed-meshheading:15465043-Bacterial Proteins, pubmed-meshheading:15465043-Binding Sites, pubmed-meshheading:15465043-Crystallography, X-Ray, pubmed-meshheading:15465043-Eukaryotic Cells, pubmed-meshheading:15465043-Fungal Proteins, pubmed-meshheading:15465043-Ligands, pubmed-meshheading:15465043-Macromolecular Substances, pubmed-meshheading:15465043-Models, Molecular, pubmed-meshheading:15465043-Molecular Sequence Data, pubmed-meshheading:15465043-NAD, pubmed-meshheading:15465043-Phosphonic Acids, pubmed-meshheading:15465043-Phosphorus-Oxygen Lyases, pubmed-meshheading:15465043-Prokaryotic Cells, pubmed-meshheading:15465043-Protein Conformation, pubmed-meshheading:15465043-Sequence Alignment, pubmed-meshheading:15465043-Staphylococcus aureus
pubmed:year
2004
pubmed:articleTitle
Comparison of ligand-induced conformational changes and domain closure mechanisms, between prokaryotic and eukaryotic dehydroquinate synthases.
pubmed:affiliation
Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't