Related ArticlesNMR solution structure of the antitumor compound PT523 and NADPH in the ternary complex with human dihydrofolate reductase.
Biochemistry. 1997 Apr 15;36(15):4399-411
Authors: Johnson JM, Meiering EM, Wright JE, Pardo J, Rosowsky A, Wagner G
The antitumor compound PT523 [N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L- ornithine] was found to have an inhibition constant (K(i)) of 0.35 +/- 0.10 pM against human dihydrofolate reductase (hDHFR), 15-fold lower than that of the classical antifolate drug methotrexate (MTX). The structure of PT523 bound to hDHFR and hDHFR-NADPH was investigated using multinuclear NMR techniques. NMR data indicate that the binary complex has two distinct conformations in solution which are in slow exchange and that the addition of NADPH stabilizes the ternary complex in a single bound state. Comparison of resonance assignments in the PT523 and MTX ternary complexes revealed that substantial protein chemical shift differences are limited to small regions of hDHFR tertiary structure. A restrained molecular dynamics and energy minimization protocol was performed for the hDHFR-PT523-NADPH complex, using 185 NOE restraints (33 intermolecular) to define the ligand-binding region. The positions of the pteridine and pABA rings of PT523 and the nicotinamide and ribose rings of NADPH are well defined in the solution structures (RMSD = 0.59 A) and are consistent with previously determined structures of DHFR complexes. The N(delta)-hemiphthaloyl-L-ornithine group of PT523 is less well defined, and the calculated model structures suggest the hemiphthaloyl ring may adopt more than one conformation in solution. Contacts between the hemiphthaloyl ring and hDHFR, which are not possible in the hDHFR-MTX-NADPH complex, may explain the greater inhibition potency of PT523.
[NMR paper] NMR and luminescence studies on the formation of ternary adducts between HSA and Ln(I
NMR and luminescence studies on the formation of ternary adducts between HSA and Ln(III)-malonate complexes.
Related Articles NMR and luminescence studies on the formation of ternary adducts between HSA and Ln(III)-malonate complexes.
Biochim Biophys Acta. 1998 Jun 11;1385(1):7-16
Authors: Aime S, Bettinelli M, Ferrari M, Razzano E, Terreno E
At physiological pH and in the presence of an excess of malonate ligand (MAL), the lanthanide ions (Ln=Eu(III), Gd(III) and Tb(III)) are under the form of -. Upon addition of human serum albumin (HSA),...
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[NMR paper] NMR solution structure of the antitumor compound PT523 and NADPH in the ternary compl
NMR solution structure of the antitumor compound PT523 and NADPH in the ternary complex with human dihydrofolate reductase.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-acspubs.jpg Related Articles NMR solution structure of the antitumor compound PT523 and NADPH in the ternary complex with human dihydrofolate reductase.
Biochemistry. 1997 Apr 15;36(15):4399-411
Authors: Johnson JM, Meiering EM, Wright JE, Pardo J, Rosowsky A, Wagner G
The antitumor compound PT523 was found to have an inhibition constant (K(i))...
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08-22-2010 03:03 PM
[NMR paper] Evidence for a ternary complex formed between flavodoxin and cytochrome c3: 1H-NMR an
Evidence for a ternary complex formed between flavodoxin and cytochrome c3: 1H-NMR and molecular modeling studies.
Related Articles Evidence for a ternary complex formed between flavodoxin and cytochrome c3: 1H-NMR and molecular modeling studies.
Biochemistry. 1994 May 31;33(21):6394-407
Authors: Palma PN, Moura I, LeGall J, Van Beeumen J, Wampler JE, Moura JJ
Small electron-transfer proteins such as flavodoxin (16 kDa) and the tetraheme cytochrome c3 (13 kDa) have been used to mimic, in vitro, part of the complex electron-transfer chain...
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[Nature network NMR forum] Journal club: structure of the ternary Prp31:15.5K:U4 snRNA complex (1 reply)
Journal club: structure of the ternary Prp31:15.5K:U4 snRNA complex (1 reply)
I would like to start the “journal club” section of the NMR forum by presenting my favorite paper from the recent literature.
The paper (in this weeks issue of Science) is, in my opinion at least, a perfect example of the ability of NMR to contribute to the structural analysis of a challenging RNA-protein complex
I chose this high-impact paper because the combination of biochemistry, NMR, and crystallography on a ternary complex is how I would like to tackle a challenging project that I am...
NMR solution structure of the antitumor compound PT523 and NADPH in the ternary compl
Linear Mode
