Linked Life Data

19606873

Source:http://linkedlifedata.com/resource/pubmed/id/19606873

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
31
pubmed:dateCreated
2009-9-2
pubmed:abstractText
As it is becoming accepted that allosteric regulation can occur through a change in local conformational equilibria as opposed to a change in overall static structure, a thorough description of the structural aspects of these types of mechanisms will be essential to understanding this fundamental biological process. Here we report the experimental identification of key regions of conformational perturbation in the allosteric network of a large (144 kDa), multidomain enzyme by use of solution-phase hydrogen/deuterium exchange. Large perturbations in the regulatory domain induced by effector molecule binding are linked to a very specific, targeted perturbation in the active site, some 50 A away. Binding of L-leucine to an enzyme variant (Y410F) that is kinetically insensitive to effector binding was shown to elicit similar changes in the regulatory domain, but perturbs an alternate region of the catalytic domain, consistent with the proposed allosteric mechanism. These results comprise one of the first reports of an experimentally mapped allosteric mechanism in a protein of this size and provide necessary information to be used toward the development of allostery-based drugs or enzymes with engineered regulatory properties.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7457-64
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Mapping of the allosteric network in the regulation of alpha-isopropylmalate synthase from Mycobacterium tuberculosis by the feedback inhibitor L-leucine: solution-phase H/D exchange monitored by FT-ICR mass spectrometry.
pubmed:affiliation
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural