The Experts below are selected from a list of 129 Experts worldwide ranked by ideXlab platform
Anthony Maxwell - One of the best experts on this subject based on the ideXlab platform.
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Nucleotide binding to the 43-kilodalton N-terminal fragment of the DNA gyrase B protein.
Biochemistry, 1995Co-Authors: Janid A. Ali, George Orphanides, Anthony MaxwellAbstract:The binding of ADPNP (5'-adenylyl beta,gamma-imidodiphosphate) to the 43-kDa N-terminal fragment of the DNA gyrase B protein is found to stabilize a dimer of the protein. Analysis of the kinetics of binding of ADPNP to the fragment suggests that protein dimers can contain 1 or 2 molecules of bound nucleotide. ATP, ADP, or Coumarin Drugs inhibit the binding of ADPNP. The rate of dissociation of ADPNP from the 43-kDa protein is found to be very slow and unaffected by the presence of other nucleotides. These data can be accommodated by a scheme in which the 43-kDa monomer forms a short-lived complex with ADPNP that can be converted into long-lived dimer complexes containing either 1 or 2 molecules of bound ADPNP; dimer formation with 2 bound ADPNPs is strongly favored. Coumarin Drugs inhibit the binding of ADPNP to the 43-kDa fragment, with novobiocin binding to the protein with a stoichiometry of 1:1 and coumermycin binding with a stoichiometry of 0.5:1.
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the 24 kda n terminal sub domain of the dna gyrase b protein binds Coumarin Drugs
Molecular Microbiology, 1994Co-Authors: Jane E Gilbert, Anthony MaxwellAbstract:Summary A number of lines of evidence suggest that the N-terminal sub-domain of the DNA gyrase B protein contains the binding site for the Coumarin antibiotics. We have engineered a clone which encodes a 24 kDa protein which represents this domain. Bacteria which overproduce this protein show an elevated level of resistance to Coumarins, suggestive of binding of the 24 kDa protein to the Drugs In vivo. In vitro we find that the 24 kDa protein does not interact with the gyrase A or B proteins or with DNA, and fails to hydrolyse ATP or show significant binding to ATP, ADP or ADPNP. However, we show that the 24 kDa protein binds Coumarin Drugs as tightly as the Intact B protein. A number of experiments suggest that the Interaction of the Coumarins with the protein is predominantly hydrophobic in nature.
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The 24 kDa N‐terminal sub‐domain of the DNA gyrase B protein binds Coumarin Drugs
Molecular microbiology, 1994Co-Authors: E. Jane Gilbert, Anthony MaxwellAbstract:Summary A number of lines of evidence suggest that the N-terminal sub-domain of the DNA gyrase B protein contains the binding site for the Coumarin antibiotics. We have engineered a clone which encodes a 24 kDa protein which represents this domain. Bacteria which overproduce this protein show an elevated level of resistance to Coumarins, suggestive of binding of the 24 kDa protein to the Drugs In vivo. In vitro we find that the 24 kDa protein does not interact with the gyrase A or B proteins or with DNA, and fails to hydrolyse ATP or show significant binding to ATP, ADP or ADPNP. However, we show that the 24 kDa protein binds Coumarin Drugs as tightly as the Intact B protein. A number of experiments suggest that the Interaction of the Coumarins with the protein is predominantly hydrophobic in nature.
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The 43-kilodalton N-terminal fragment of the DNA gyrase B protein hydrolyzes ATP and binds Coumarin Drugs
Biochemistry, 1993Co-Authors: Janid A. Ali, Andrew P. Jackson, Alison J. Howells, Anthony MaxwellAbstract:We have cloned and overexpressed a gene encoding a 43-kDa protein corresponding to the N-terminal fragment of the DNA gyrase B subunit. We show that this protein hydrolyzes ATP and binds Coumarin Drugs. The hydrolysis of ATP shows distinctly non-Michaelis-Menten kinetics and is consistent with a scheme in which the active form of the protein is a dimer, a conclusion supported by molecular weight studies. The Coumarin Drugs bind very tightly to the 43-kDa fragment, with novobiocin binding to the protein monomer and coumermycin A1 apparently inducing the formation of a dimer. The implications of these results with respect to the mechanism of supercoiling by DNA gyrase and the inhibition of gyrase by Coumarin Drugs are discussed.
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The interaction between Coumarin Drugs and DNA gyrase.
Molecular microbiology, 1993Co-Authors: Anthony MaxwellAbstract:The Coumarin group of antibiotics have as their target the bacterial enzyme DNA gyrase. The Drugs bind to the B subunit of gyrase and inhibit DNA supercoiling by blocking the ATPase activity. Recent data show that the binding site for the Drugs lies within the N-terminal part of the B protein, and individual amino acids involved in Coumarin interaction are being identified. The mode of inhibition of the gyrase ATPase reaction by Coumarins is unlikely to be simple competitive inhibition, and the Drugs may act by stabilizing a conformation of the enzyme with low affinity for ATP.
M Huang - One of the best experts on this subject based on the ideXlab platform.
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impact of the cyp4f2 p v433m polymorphism on Coumarin dose requirement systematic review and meta analysis
Clinical Pharmacology & Therapeutics, 2012Co-Authors: Elisa Danese, Larisa H. Cavallari, Allan E. Rettie, Martina Montagnana, Julie A Johnson, Carlofederico Zambon, Steven A Lubitz, Guilherme Suarezkurtz, L Zhao, M HuangAbstract:A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on Coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily Coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I-2 = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to Coumarin Drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms. (Less)
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impact of the cyp4f2 p v433m polymorphism on Coumarin dose requirement systematic review and meta analysis
Clinical Pharmacology & Therapeutics, 2012Co-Authors: Elisa Danese, Larisa H. Cavallari, Allan E. Rettie, Martina Montagnana, Julie A Johnson, Carlofederico Zambon, Steven A Lubitz, Guilherme Suarezkurtz, L Zhao, M HuangAbstract:A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on Coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily Coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I(2) = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to Coumarin Drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms.
Elisa Danese - One of the best experts on this subject based on the ideXlab platform.
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impact of the cyp4f2 p v433m polymorphism on Coumarin dose requirement systematic review and meta analysis
Clinical Pharmacology & Therapeutics, 2012Co-Authors: Elisa Danese, Larisa H. Cavallari, Allan E. Rettie, Martina Montagnana, Julie A Johnson, Carlofederico Zambon, Steven A Lubitz, Guilherme Suarezkurtz, L Zhao, M HuangAbstract:A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on Coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily Coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I-2 = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to Coumarin Drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms. (Less)
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impact of the cyp4f2 p v433m polymorphism on Coumarin dose requirement systematic review and meta analysis
Clinical Pharmacology & Therapeutics, 2012Co-Authors: Elisa Danese, Larisa H. Cavallari, Allan E. Rettie, Martina Montagnana, Julie A Johnson, Carlofederico Zambon, Steven A Lubitz, Guilherme Suarezkurtz, L Zhao, M HuangAbstract:A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on Coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily Coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I(2) = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to Coumarin Drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms.
Guilherme Suarezkurtz - One of the best experts on this subject based on the ideXlab platform.
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impact of the cyp4f2 p v433m polymorphism on Coumarin dose requirement systematic review and meta analysis
Clinical Pharmacology & Therapeutics, 2012Co-Authors: Elisa Danese, Larisa H. Cavallari, Allan E. Rettie, Martina Montagnana, Julie A Johnson, Carlofederico Zambon, Steven A Lubitz, Guilherme Suarezkurtz, L Zhao, M HuangAbstract:A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on Coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily Coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I-2 = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to Coumarin Drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms. (Less)
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impact of the cyp4f2 p v433m polymorphism on Coumarin dose requirement systematic review and meta analysis
Clinical Pharmacology & Therapeutics, 2012Co-Authors: Elisa Danese, Larisa H. Cavallari, Allan E. Rettie, Martina Montagnana, Julie A Johnson, Carlofederico Zambon, Steven A Lubitz, Guilherme Suarezkurtz, L Zhao, M HuangAbstract:A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on Coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily Coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I(2) = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to Coumarin Drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms.
Larisa H. Cavallari - One of the best experts on this subject based on the ideXlab platform.
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impact of the cyp4f2 p v433m polymorphism on Coumarin dose requirement systematic review and meta analysis
Clinical Pharmacology & Therapeutics, 2012Co-Authors: Elisa Danese, Larisa H. Cavallari, Allan E. Rettie, Martina Montagnana, Julie A Johnson, Carlofederico Zambon, Steven A Lubitz, Guilherme Suarezkurtz, L Zhao, M HuangAbstract:A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on Coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily Coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I-2 = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to Coumarin Drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms. (Less)
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impact of the cyp4f2 p v433m polymorphism on Coumarin dose requirement systematic review and meta analysis
Clinical Pharmacology & Therapeutics, 2012Co-Authors: Elisa Danese, Larisa H. Cavallari, Allan E. Rettie, Martina Montagnana, Julie A Johnson, Carlofederico Zambon, Steven A Lubitz, Guilherme Suarezkurtz, L Zhao, M HuangAbstract:A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on Coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily Coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I(2) = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to Coumarin Drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms.
