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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1994-2-18
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pubmed:abstractText |
Apo-dihydrofolate reductase from Escherichia coli samples two distinct environments slowly on the NMR time scale at room temperature. Several assigned resonances belong to residues in, or proximal to, a loop (loop I) which is comprised of residues 9-24. This exchange process was altered (either removed or made fast on the NMR time scale) by deleting three hairpin turn forming residues from the loop and filling the gap with a single glycine [Li, L., Falzone, C. J., Wright, P. E., & Benkovic, S. J. (1992) Biochemistry 31, 7826-7833]. An approximate value of 35 s-1 for the exchange rate associated with loop I in apo-DHFR was obtained in two-dimensional nuclear Overhauser spectra by analyzing the time dependence of the cross-peak volume for N epsilon H of Trp-22, a residue which is located in this loop and which has resolved cross-peaks. Owing to the critical role that this loop plays in catalysis, the correspondence between this rate of conformational exchange and off-rates for tetrahydrofolate and the reduced nicotinamide cofactor from product and substrate complexes suggests that loop movement may be a limiting factor in substrate turnover.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0006-2960
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
33
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
439-42
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8286374-Catalysis,
pubmed-meshheading:8286374-Crystallization,
pubmed-meshheading:8286374-Crystallography, X-Ray,
pubmed-meshheading:8286374-Escherichia coli,
pubmed-meshheading:8286374-Folic Acid,
pubmed-meshheading:8286374-Magnetic Resonance Spectroscopy,
pubmed-meshheading:8286374-Methotrexate,
pubmed-meshheading:8286374-Molecular Structure,
pubmed-meshheading:8286374-NADP,
pubmed-meshheading:8286374-Protein Conformation,
pubmed-meshheading:8286374-Tetrahydrofolate Dehydrogenase
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pubmed:year |
1994
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pubmed:articleTitle |
Dynamics of a flexible loop in dihydrofolate reductase from Escherichia coli and its implication for catalysis.
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pubmed:affiliation |
Department of Chemistry, Pennsylvania State University, University Park 16802.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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