Dihydrofolate reductase, domain

Toyoda T, Brobey RKB, Sano G, Horii T, Tomioka N, Itai Akiko. Lead discovery of inhibitors of the dihydrofolate reductase domain of Plasmodium falciparum dihydrofolate reductase-thymidylate synthase. Biochem Biophys Res Commun 1997 235 515-19. 

Harris JB, Grubb BD, Maltin CA, Dixon R (2000) The neurotoxicity of the venom phospholipases A(2), notexin and taipoxin. Exp Neurol 161 517-26 Haug G, Wilde C, Leemhuis J, Meyer DK, Aktories K et al. (2003) Cellular uptake of Clostridium botulinum C2 toxin membrane translocation of a fusion toxin requires unfolding of its dihydrofolate reductase domain. Biochemistry 42 15284-91 Hauschild A (1993) Epidemiology of human foodborne botulism. In Hauschild A, Dodds KL (eds) Clostridium botulinum ecology and control in foods. Marcel Dekker, Inc. New York, pp 69-104... 

Res. Commun., 235, 515 (1997). Lead Discovery of Inhibitors of the Dihydrofolate Reductase Domain of Plasmodium falciparum Dihydrofolate Reductase-Thymidylate... 

Studies using free energy calculations for the design and analysis of potential drug candidates are reviewed in section five. The chapters in this section cover drug discovery programs targeting fructose 1,6-bisphosphatase (diabetes), COX-2 (inflammation), SRC SH2 domain (osteoporosis and cancer), HIV reverse transcriptase (AIDS), HIV-1 protease (AIDS), thymidylate synthase (cancer), dihydrofolate reductase (cancer) and adenosine deaminase (immunosuppression, myocardial ischemia). 

Arabinose-binding protein domains 1 and 2 Dihydrofolate reductase Adenylate kinase Rhodanese domains 1 and 2 Glutathione reductase domains 1 and 2 Phosphoglycerate mutase Phosphoglycerate kinase domain 2 Pyruvate kinase domain 3 Hexokinase domains 1 and 2 Catalase domain 3 Aspartate aminotransferase... 

Pelletier, J. N., Campbell-Valois, F. X., and Michnick, S. W. (1998). Oligomerization domain-directed reassembly of active dihydrofolate reductase from rationally designed fragments. Proc. Natl. Acad. Sci. USA, 95, 12141-12146. 

Diisopropylfluorophosphate diisopropylphosphorofluoridate Dihydrofolate reductase Dihydroorotase domain Dihydroorotase... 

The Michnick group has also developed an elegant split-reporter system, based on reconstitution of dihydrofolate reductase (DHFR) (41). In this system, cell survival requires functional DHFR thus, a successful protein-protein interaction can be identified readily by selection. This system has been applied to the identification of peptide sequences that bind the Ras-binding domain of Raf (42). 

Campbell-Valois FX, Michnick SW. Synthesis of degenerated libraries of the ras-binding domain of raf and rapid selection of fast-folding and stable clones with the dihydrofolate reductase protein fragment complementation assay. Methods Mol. Biol. 2007 352 249-274. 

P.H. Liang and K.S. Anderson. 1998. Substrate channeling and domain-domain interactions in bifunctional thymidylate synthase-dihydrofolate reductase Biochemistry 37 12195-12205. (PubMed)... 

The deaminase domains are members of the cytosine deaminase superfamily. They bind catalytically essential Zn ions through complexation by one histidine and two cysteine residues. The reductase domains are members of the dihydrofolate reductase superfamily. In fact, the reactions catalyzed by pyrimidine reductase and dihydrofolate reductase are closely similar. Early in vivo work had shown that the hydride ion is incorporated into the 1 position. ... 

The dihydrofolate reductases of animals and of certain eubacteria are monomeric proteins with molecular weights around 20 kDa. Other eubacteria, ciliate, protozoa, plants, and certain viruses specify bifunctional proteins (DHFR-TS) characterized by dihydrofolate reductase and thymidylate synthetase domains. 

We demonstrate the latter approaeh on a small protein domain, which is homologous to proteins that are present in the protein data bank [86], As can be nicely seen in Fig. 55, rhodniin, which is homologous to other Kazal-type inhibitors, is found in the protein data bank. Here, the sequence homology is quite high. However, also structures with almost no sequence homologies are detected, as is the case for dihydrofolate reductase and D-xylose isomerase. 

Y. Y. Sham, B. Ma, C.-J. Tsai, and R. Nussinov, Proteins Struct., Punct., Bioinf., 46, 308 (2002). Thermal Unfolding Molecular Dynamics Simulation of Escherichia Coli Dihydrofolate Reductase Thermal Stability of Protein Domains and Unfolding Pathway. 

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