Related ArticlesDynamics of trimethoprim bound to dihydrofolate reductase--a deuterium NMR study.
Solid State Nucl Magn Reson. 1996 Dec;7(3):193-201
Authors: Yang QX, Huang FY, Lin TH, Gelbaum L, Howell EE, Huang TH
We have employed deuterium NMR techniques to determine the dynamics of trimethoprim (TMP) in a binary complex with dihydrofolate reductase (DHFR) or in a ternary complex with DHFR and cofactor NADP+ in the fully hydrated state. TMP was deuterated at the following positions: (2',6'-D2)TMP, (3'-Ome-D3)TMP and (3',4'-Ome-D6)TMP. Dynamics of TMP were deduced from lineshape simulation and relaxation measurements of the deuterium NMR powder spectra of the three samples obtained at various temperatures. The results showed that in the polycrystalline state the TMP molecule is very rigid. The only detectable motion is the methyl group rotation at a rate of 10(10) s-1 at 25 degrees C, as determined from simulation of the partially relaxed powder patterns. When bound to DHFR a residual deuterium quadrupole splitting of 140 kHz was observed for (2',6'-D2)TMP at temperatures up to 30 degrees C, suggesting that the benzyl ring in the bound state is also very rigid. In contrast, in the binary complex with DHFR the methoxyl groups of TMP undergo librational motion of 10(7) s-1 about the C3-O bond at an amplitude of 54 degrees for the meta methoxyl group and about the C4-O bond at an amplitude of 70 degrees and similar rate for the para methoxyl group at 30 degrees C. The presence of the cofactor, NADP+, appears to tighten up the binding pocket such that the motion freedom of TMP is more restricted. The rigidity of TMP in a protein complex as revealed by our deuterium NMR results is in accord with the tight binding of TMP to DHFR.
Thermodynamic and NMR analysis of inhibitor binding to dihydrofolate reductase.
Thermodynamic and NMR analysis of inhibitor binding to dihydrofolate reductase.
Thermodynamic and NMR analysis of inhibitor binding to dihydrofolate reductase.
Bioorg Med Chem. 2010 Dec 15;18(24):8485-92
Authors: Batruch I, Javasky E, Brown ED, Organ MG, Johnson PE
Isothermal titration calorimetry (ITC) was used to determine the thermodynamic driving force for inhibitor binding to the enzyme dihydrofolate reductase (DHFR) from Escherichia coli. 1,4-Bis-{sulfanylmethyl}-3,6-dimethyl-benzene (1) binds DHFR:NADPH with a K(d) of 13±5 nM while the...
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[NMR paper] High pressure nmr study of dihydrofolate reductase from a deep-sea bacterium Moritell
High pressure nmr study of dihydrofolate reductase from a deep-sea bacterium Moritella profunda.
Related Articles High pressure nmr study of dihydrofolate reductase from a deep-sea bacterium Moritella profunda.
Cell Mol Biol (Noisy-le-grand). 2004 Jun;50(4):311-6
Authors: Hata K, Kono R, Fujisawa M, Kitahara R, Kamatari YO, Akasaka K, Xu Y
We have investigated the effect of pressure and temperature on the structural and thermodynamic stability of a protein dihydrofolate reductase from a deep-sea bacterium Moritella profunda in its folate-bound...
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[NMR paper] The effect of hydration on the dynamics of trimethoprim bound to dihydrofolate reduct
The effect of hydration on the dynamics of trimethoprim bound to dihydrofolate reductase. A deuterium NMR study.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-cellhub.gif http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.pubmedcentral.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.gif Related Articles The effect of hydration on the dynamics of trimethoprim bound to dihydrofolate reductase. A deuterium NMR study.
Biophys J. 1993 Apr;64(4):1361-5
Authors: Yang QX, Huang FY, Huang TH, Gelbaum L
To...
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[NMR paper] Dihydrofolate reductase: sequential resonance assignments using 2D and 3D NMR and sec
Dihydrofolate reductase: sequential resonance assignments using 2D and 3D NMR and secondary structure determination in solution.
Related Articles Dihydrofolate reductase: sequential resonance assignments using 2D and 3D NMR and secondary structure determination in solution.
Biochemistry. 1991 Jun 25;30(25):6330-41
Authors: Carr MD, Birdsall B, Frenkiel TA, Bauer CJ, Jimenez-Barbero J, Polshakov VI, McCormick JE, Roberts GC, Feeney J
Three-dimensional (3D) heteronuclear NMR techniques have been used to make sequential 1H and 15N resonance...
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[NMR paper] The conformations of trimethoprim/E. coli dihydrofolate reductase complexes. A 15N an
The conformations of trimethoprim/E. coli dihydrofolate reductase complexes. A 15N and 31P NMR study.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles The conformations of trimethoprim/E. coli dihydrofolate reductase complexes. A 15N and 31P NMR study.
FEBS Lett. 1991 May 20;283(1):44-6
Authors: Huang FY, Yang QX, Huang TH, Gelbaum L, Kuyper LF
We have employed 15N and 31P NMR techniques to characterize the conformations of trimethoprim (TMP)/E. coli dihydrofolate...
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[NMR paper] NMR studies of interactions of ligands with dihydrofolate reductase.
NMR studies of interactions of ligands with dihydrofolate reductase.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles NMR studies of interactions of ligands with dihydrofolate reductase.
Biochem Pharmacol. 1990 Jul 1;40(1):141-52
Authors: Feeney J
NMR spectroscopy is a useful technique for studying interactions, conformations and dynamic processes within ligand-protein complexes. Several examples of the application of the method to studies of complexes of anti-folate...