Linked Life Data

19241473

Source:http://linkedlifedata.com/resource/pubmed/id/19241473

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-7-27
pubmed:abstractText
Nucleoside diphosphate kinases (Ndks) play an important role in a plethora of regulatory and metabolic functions. Inhibition of the B. anthracis Ndk mRNA results in the formation of nonviable aberrant spores. We report the characterization and crystal structure of the enzyme from B. anthracis nucleoside diphosphate kinase (BaNdk), the first from sporulating bacteria. The enzyme, although from a mesophilic source, is active at extremes of pH (3.5-10.5), temperature (10-95 degrees C) and ionic strength (0.25-4.0M NaCl). It exists as a hexamer that is composed of two SDS-stable trimers interacting in a back-to-back association; mutational analysis confirms that the enzyme is a histidine kinase. The high-resolution crystal structure reported here reveals an unanticipated change in the conformation of residues between 43 and 63 that also regulates substrate entry in other Ndks. A comparative structural analysis involving Ndks from seven mesophiles and three thermophiles has resulted in the delineation of the structure into relatively rigid and flexible regions. The analysis suggests that the larger number of intramolecular hydrogen bonds and to a lesser extent ionic interactions in BaNdk contributes to its high thermostability. Mutational analysis and Molecular Dynamics simulations were used to probe the role of a highly conserved Gly19 (present at the oligomeric interface in most of the Ndks). The results suggest that the mutation leads to a rigidification of those residues that facilitate substrate entry and consequently leads to a large reduction in the kinase activity. Overall, the enzyme characterization helps to understand its apparent adaptation to perform under stress conditions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1097-0134
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
76
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
496-506
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Crystal structure of the Bacillus anthracis nucleoside diphosphate kinase and its characterization reveals an enzyme adapted to perform under stress conditions.
pubmed:affiliation
Central Drug Research Institute, Lucknow, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't