Linked Life Data

15465058

Source:http://linkedlifedata.com/resource/pubmed/id/15465058

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-10-6
pubmed:abstractText
Consensus design methods have been used successfully to engineer proteins with a particular fold, and moreover to engineer thermostable exemplars of particular folds. Here, we consider how a statistical free energy approach can expand upon current methods of phylogenetic design. As an example, we have analyzed the tetratricopeptide repeat (TPR) motif, using multiple sequence alignment to identify the significance of each position in the TPR. The results provide information above and beyond that revealed by consensus design alone, especially at poorly conserved positions. A particularly striking finding is that certain residues, which TPR-peptide co-crystal structures show are in direct contact with the ligand, display a marked hypervariability. This suggests a novel means of identifying ligand-binding sites, and also implies that TPRs generally function as ligand-binding domains. Using perturbation analysis (or statistical coupling analysis), we examined site-site interactions within the TPR motif. Correlated occurrences of amino acid residues at poorly conserved positions explain how TPRs achieve their near-neutral surface charge distributions, and why a TPR designed from straight consensus has an unusually high net charge. Networks of interacting sites revealed that TPRs fall into two unrecognized families with distinct sets of interactions related to the identity of position 7 (Leu or Lys/Arg). Statistical free energy analysis provides a more complete description of "What makes a TPR a TPR?" than consensus alone, and it suggests general approaches to extend and improve the phylogenetic design of proteins.
pubmed:grant
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
731-45
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Beyond consensus: statistical free energies reveal hidden interactions in the design of a TPR motif.
pubmed:affiliation
Department of Molecular Biophysics and Biochemistry, Yale University, P.O. Box 208114, New Haven, CT 06520-8114, USA. thomas.magliery@yale.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.