Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-4-9
pubmed:databankReference
pubmed:abstractText
SlyD (sensitive to lysis D) is a putative folding helper from the bacterial cytosol and harbors prolyl isomerase and chaperone activities. We determined the solution NMR structure of a truncated version of SlyD (1-165) from Escherichia coli (SlyD*) that lacks the presumably unstructured C-terminal tail. SlyD* consists of two well-separated domains: the FKBP domain, which harbors the prolyl isomerase activity, and the insert-in-flap (IF) domain, which harbors the chaperone activity. The IF domain is inserted into a loop of the FKBP domain near the prolyl isomerase active site. The NMR structure of SlyD* showed no distinct orientation of the two domains relative to each other. In the FKBP domain, Tyr68 points into the active site, which might explain the lowered intrinsic prolyl isomerase activity and the much lower FK506 binding affinity of the protein compared with archetype human FKBP12 (human FK506 binding protein with 12 kDa). The thermodynamics and kinetics of substrate binding by SlyD* were quantified by fluorescence resonance energy transfer. NMR titration experiments revealed that the IF domain recognizes and binds unfolded or partially folded proteins and peptides. Insulin aggregation is markedly slowed by SlyD* as evidenced by two-dimensional NMR spectroscopy in real time, probably due to SlyD* binding to denatured insulin. The capacity of the IF domain to establish an initial encounter-collision complex, together with the flexible orientation of the two interacting domains, makes SlyD* a very powerful catalyst of protein folding.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1089-8638
pubmed:author
pubmed:issnType
Electronic
pubmed:day
27
pubmed:volume
387
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
295-305
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:19356587-Amino Acid Sequence, pubmed-meshheading:19356587-Binding Sites, pubmed-meshheading:19356587-Dithiothreitol, pubmed-meshheading:19356587-Escherichia coli, pubmed-meshheading:19356587-Escherichia coli Proteins, pubmed-meshheading:19356587-Insulin, pubmed-meshheading:19356587-Kinetics, pubmed-meshheading:19356587-Magnetic Resonance Spectroscopy, pubmed-meshheading:19356587-Molecular Chaperones, pubmed-meshheading:19356587-Molecular Sequence Data, pubmed-meshheading:19356587-Mutant Proteins, pubmed-meshheading:19356587-Peptidylprolyl Isomerase, pubmed-meshheading:19356587-Protein Structure, Quaternary, pubmed-meshheading:19356587-Protein Structure, Secondary, pubmed-meshheading:19356587-Protein Structure, Tertiary, pubmed-meshheading:19356587-Solutions, pubmed-meshheading:19356587-Substrate Specificity, pubmed-meshheading:19356587-Thermodynamics
pubmed:year
2009
pubmed:articleTitle
NMR solution structure of SlyD from Escherichia coli: spatial separation of prolyl isomerase and chaperone function.
pubmed:affiliation
Institut für Physik, Fachgruppe Biophysik, Martin-Luther-Universität Halle-Wittenberg, D-06099 Halle (Saale), Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't