Source:http://linkedlifedata.com/resource/pubmed/id/17935333
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
45
|
pubmed:dateCreated |
2007-11-7
|
pubmed:abstractText |
A fundamental question in protein chemistry is how the native energy landscape of enzymes enables efficient catalysis of chemical reactions. Adenylate kinase is a small monomeric enzyme that catalyzes the reversible conversion of AMP and ATP into two ADP molecules. Previous structural studies have revealed that substrate binding is accompanied by large rate-limiting spatial displacements of both the ATP and AMP binding motifs. In this report a solution-state NMR approach was used to probe the native energy landscape of adenylate kinase in its free form, in complex with its natural substrates, and in the presence of a tight binding inhibitor. Binding of ATP induces a dynamic equilibrium in which the ATP binding motif populates both the open and the closed conformations with almost equal populations. A similar scenario is observed for AMP binding, which induces an equilibrium between open and closed conformations of the AMP binding motif. These ATP- and AMP-bound structural ensembles represent complexes that exist transiently during catalysis. Simultaneous binding of AMP and ATP is required to force both substrate binding motifs to close cooperatively. In addition, a previously unknown unidirectional energetic coupling between the ATP and AMP binding sites was discovered. On the basis of these and previous results, we propose that adenylate kinase belongs to a group of enzymes whose substrates act to shift pre-existing equilibria toward catalytically active states.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Nov
|
pubmed:issn |
0002-7863
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
14
|
pubmed:volume |
129
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
14003-12
|
pubmed:meshHeading |
pubmed-meshheading:17935333-Adenosine Diphosphate,
pubmed-meshheading:17935333-Adenosine Monophosphate,
pubmed-meshheading:17935333-Adenosine Triphosphate,
pubmed-meshheading:17935333-Adenylate Kinase,
pubmed-meshheading:17935333-Catalysis,
pubmed-meshheading:17935333-Magnetic Resonance Spectroscopy,
pubmed-meshheading:17935333-Mutagenesis, Site-Directed,
pubmed-meshheading:17935333-Protein Conformation,
pubmed-meshheading:17935333-Protein Structure, Tertiary,
pubmed-meshheading:17935333-Reference Standards
|
pubmed:year |
2007
|
pubmed:articleTitle |
NMR identification of transient complexes critical to adenylate kinase catalysis.
|
pubmed:affiliation |
Department of Chemistry, University of Umeå, SE-901 87 Umeå, Sweden.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|