naphthoquinones and teriflunomide

naphthoquinones has been researched along with teriflunomide* in 1 studies

Other Studies

1 other study(ies) available for naphthoquinones and teriflunomide

Article	Year
Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain. Protein science : a publication of the Protein Society, 2004, Volume: 13, Issue:4 The flavin enzyme dihydroorotate dehydrogenase (DHOD; EC 1.3.99.11) catalyzes the oxidation of dihydroorotate to orotate, the fourth step in the de novo pyrimidine biosynthesis of UMP. The enzyme is a promising target for drug design in different biological and clinical applications for cancer and arthritis. The first crystal structure of the class 2 dihydroorotate dehydrogenase from rat has been determined in complex with its two inhibitors brequinar and atovaquone. These inhibitors have shown promising results as anti-proliferative, immunosuppressive, and antiparasitic agents. A unique feature of the class 2 DHODs is their N-terminal extension, which folds into a separate domain comprising two alpha-helices. This domain serves as the binding site for the two inhibitors and the respiratory quinones acting as the second substrate for the class 2 DHODs. The orientation of the first N-terminal helix is very different in the two complexes of rat DHOD (DHODR). Binding of atovaquone causes a 12 A movement of the first residue in the first alpha-helix. Based on the information from the two structures of DHODR, a model for binding of the quinone and the residues important for the interactions could be defined. His 56 and Arg 136, which are fully conserved in all class 2 DHODs, seem to play a key role in the interaction with the electron acceptor. The differences between the membrane-bound rat DHOD and membrane-associated class 2 DHODs exemplified by the Escherichia coli DHOD has been investigated by GRID computations of the hydrophobic probes predicted to interact with the membrane. Topics: Amino Acid Sequence; Aniline Compounds; Animals; Atovaquone; Biphenyl Compounds; Catalysis; Crotonates; Crystallography, X-Ray; Dihydroorotate Dehydrogenase; Drug Design; Enzyme Inhibitors; Hydrogen Bonding; Hydroxybutyrates; Immunosuppressive Agents; Models, Molecular; Molecular Sequence Data; Molecular Structure; Naphthoquinones; Nitriles; Orotic Acid; Oxidoreductases Acting on CH-CH Group Donors; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Rats; Sequence Alignment; Substrate Specificity; Toluidines	2004

Article

Year

Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain.

Protein science : a publication of the Protein Society, 2004, Volume: 13, Issue:4

The flavin enzyme dihydroorotate dehydrogenase (DHOD; EC 1.3.99.11) catalyzes the oxidation of dihydroorotate to orotate, the fourth step in the de novo pyrimidine biosynthesis of UMP. The enzyme is a promising target for drug design in different biological and clinical applications for cancer and arthritis. The first crystal structure of the class 2 dihydroorotate dehydrogenase from rat has been determined in complex with its two inhibitors brequinar and atovaquone. These inhibitors have shown promising results as anti-proliferative, immunosuppressive, and antiparasitic agents. A unique feature of the class 2 DHODs is their N-terminal extension, which folds into a separate domain comprising two alpha-helices. This domain serves as the binding site for the two inhibitors and the respiratory quinones acting as the second substrate for the class 2 DHODs. The orientation of the first N-terminal helix is very different in the two complexes of rat DHOD (DHODR). Binding of atovaquone causes a 12 A movement of the first residue in the first alpha-helix. Based on the information from the two structures of DHODR, a model for binding of the quinone and the residues important for the interactions could be defined. His 56 and Arg 136, which are fully conserved in all class 2 DHODs, seem to play a key role in the interaction with the electron acceptor. The differences between the membrane-bound rat DHOD and membrane-associated class 2 DHODs exemplified by the Escherichia coli DHOD has been investigated by GRID computations of the hydrophobic probes predicted to interact with the membrane.

Topics: Amino Acid Sequence; Aniline Compounds; Animals; Atovaquone; Biphenyl Compounds; Catalysis; Crotonates; Crystallography, X-Ray; Dihydroorotate Dehydrogenase; Drug Design; Enzyme Inhibitors; Hydrogen Bonding; Hydroxybutyrates; Immunosuppressive Agents; Models, Molecular; Molecular Sequence Data; Molecular Structure; Naphthoquinones; Nitriles; Orotic Acid; Oxidoreductases Acting on CH-CH Group Donors; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Rats; Sequence Alignment; Substrate Specificity; Toluidines

2004