The Experts below are selected from a list of 1287 Experts worldwide ranked by ideXlab platform
Philip J Hogg - One of the best experts on this subject based on the ideXlab platform.
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the tumour metabolism inhibitors gsao and penao react with cysteines 57 and 257 of mitochondrial adenine nucleotide translocase
Cancer Cell International, 2012Co-Authors: Danielle Park, Joyce Chiu, Gabriel G Perrone, Pierre J Dilda, Philip J HoggAbstract:Background: GSAO (4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid) and PENAO (4-(N-(Spenicillaminylacetyl)amino) phenylarsonous acid) are tumour metabolism inhibitors that target adenine nucleotide translocase (ANT) of the inner-mitochondrial membrane. Both compounds are currently being trialled in patients with solid tumours. The trivalent Arsenical moiety of GSAO and PENAO reacts with two matrix facing cysteine residues of ANT, inactivating the transporter. This leads to proliferation arrest and death of tumour and tumoursupporting cells. Results: The two reactive ANT cysteine residues have been identified in this study by expressing cysteine mutants of human ANT1 in Saccharomyces cerevisiae and measuring interaction with the Arsenical moiety of GSAO and PENAO. The Arsenic Atom of both compounds cross-links cysteine residues 57 and 257 of human ANT1. Conclusions: The sulphur Atoms of these two cysteines are 20 A apart in the crystal structures of ANT and the optimal spacing of cysteine thiolates for reaction with As (III) is 3-4 A. This implies that a significant conformational change in ANT is required for the organoArsenicals to react with cysteines 57 and 257. This conformational change may relate to the selectivity of the compounds for proliferating cells.
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the tumour metabolism inhibitors gsao and penao react with cysteines 57 and 257 of mitochondrial adenine nucleotide translocase
Cancer Cell International, 2012Co-Authors: Danielle Park, Joyce Chiu, Gabriel G Perrone, Pierre J Dilda, Philip J HoggAbstract:GSAO (4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid) and PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid) are tumour metabolism inhibitors that target adenine nucleotide translocase (ANT) of the inner-mitochondrial membrane. Both compounds are currently being trialled in patients with solid tumours. The trivalent Arsenical moiety of GSAO and PENAO reacts with two matrix facing cysteine residues of ANT, inactivating the transporter. This leads to proliferation arrest and death of tumour and tumour-supporting cells. The two reactive ANT cysteine residues have been identified in this study by expressing cysteine mutants of human ANT1 in Saccharomyces cerevisiae and measuring interaction with the Arsenical moiety of GSAO and PENAO. The Arsenic Atom of both compounds cross-links cysteine residues 57 and 257 of human ANT1. The sulphur Atoms of these two cysteines are 20 A apart in the crystal structures of ANT and the optimal spacing of cysteine thiolates for reaction with As (III) is 3-4 A. This implies that a significant conformational change in ANT is required for the organoArsenicals to react with cysteines 57 and 257. This conformational change may relate to the selectivity of the compounds for proliferating cells.
Su Xiao-dong - One of the best experts on this subject based on the ideXlab platform.
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Get Phases from Arsenic Anomalous Scattering: de novo SAD Phasing of Two Protein Structures Crystallized in Cacodylate Buffer
plos one, 2011Co-Authors: Liu Xiang, Zhang Heng, Wang Xiao-jun, Li Lan-fen, Su Xiao-dongAbstract:The crystal structures of two proteins, a putative pyrazinamidase/nicotinamidase from the dental pathogen Streptococcus mutans (SmPncA) and the human caspase-6 (Casp6), were solved by de novo Arsenic single-wavelength anomalous diffraction (As-SAD) phasing method. Arsenic (As), an uncommonly used element in SAD phasing, was covalently introduced into proteins by cacodylic acid, the buffering agent in the crystallization reservoirs. In SmPncA, the only cysteine was bound to dimethylarsinoyl, which is a pentavalent Arsenic group (As (V)). This Arsenic Atom and a protein-bound zinc Atom both generated anomalous signals. The predominant contribution, however, was from the As anomalous signals, which were sufficient to phase the SmPncA structure alone. In Casp6, four cysteines were found to bind cacodyl, a trivalent Arsenic group (As (III)), in the presence of the reducing agent, dithiothreitol (DTT), and Arsenic Atoms were the only anomalous scatterers for SAD phasing. Analyses and discussion of these two As-SAD phasing examples and comparison of As with other traditional heavy Atoms that generate anomalous signals, together with a few Arsenic-based de novo phasing cases reported previously strongly suggest that As is an ideal anomalous scatterer for SAD phasing in protein crystallography.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000294686100025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Multidisciplinary SciencesSCI(E)PubMed6ARTICLE9e24227
Xiao-jun Wang - One of the best experts on this subject based on the ideXlab platform.
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Get phases from Arsenic anomalous scattering: de novo SAD phasing of two protein structures crystallized in cacodylate buffer.
PloS one, 2011Co-Authors: Xiang Liu, Heng Zhang, Xiao-jun WangAbstract:The crystal structures of two proteins, a putative pyrazinamidase/nicotinamidase from the dental pathogen Streptococcus mutans (SmPncA) and the human caspase-6 (Casp6), were solved by de novo Arsenic single-wavelength anomalous diffraction (As-SAD) phasing method. Arsenic (As), an uncommonly used element in SAD phasing, was covalently introduced into proteins by cacodylic acid, the buffering agent in the crystallization reservoirs. In SmPncA, the only cysteine was bound to dimethylarsinoyl, which is a pentavalent Arsenic group (As (V)). This Arsenic Atom and a protein-bound zinc Atom both generated anomalous signals. The predominant contribution, however, was from the As anomalous signals, which were sufficient to phase the SmPncA structure alone. In Casp6, four cysteines were found to bind cacodyl, a trivalent Arsenic group (As (III)), in the presence of the reducing agent, dithiothreitol (DTT), and Arsenic Atoms were the only anomalous scatterers for SAD phasing. Analyses and discussion of these two As-SAD phasing examples and comparison of As with other traditional heavy Atoms that generate anomalous signals, together with a few Arsenic-based de novo phasing cases reported previously strongly suggest that As is an ideal anomalous scatterer for SAD phasing in protein crystallography.
Danielle Park - One of the best experts on this subject based on the ideXlab platform.
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the tumour metabolism inhibitors gsao and penao react with cysteines 57 and 257 of mitochondrial adenine nucleotide translocase
Cancer Cell International, 2012Co-Authors: Danielle Park, Joyce Chiu, Gabriel G Perrone, Pierre J Dilda, Philip J HoggAbstract:Background: GSAO (4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid) and PENAO (4-(N-(Spenicillaminylacetyl)amino) phenylarsonous acid) are tumour metabolism inhibitors that target adenine nucleotide translocase (ANT) of the inner-mitochondrial membrane. Both compounds are currently being trialled in patients with solid tumours. The trivalent Arsenical moiety of GSAO and PENAO reacts with two matrix facing cysteine residues of ANT, inactivating the transporter. This leads to proliferation arrest and death of tumour and tumoursupporting cells. Results: The two reactive ANT cysteine residues have been identified in this study by expressing cysteine mutants of human ANT1 in Saccharomyces cerevisiae and measuring interaction with the Arsenical moiety of GSAO and PENAO. The Arsenic Atom of both compounds cross-links cysteine residues 57 and 257 of human ANT1. Conclusions: The sulphur Atoms of these two cysteines are 20 A apart in the crystal structures of ANT and the optimal spacing of cysteine thiolates for reaction with As (III) is 3-4 A. This implies that a significant conformational change in ANT is required for the organoArsenicals to react with cysteines 57 and 257. This conformational change may relate to the selectivity of the compounds for proliferating cells.
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the tumour metabolism inhibitors gsao and penao react with cysteines 57 and 257 of mitochondrial adenine nucleotide translocase
Cancer Cell International, 2012Co-Authors: Danielle Park, Joyce Chiu, Gabriel G Perrone, Pierre J Dilda, Philip J HoggAbstract:GSAO (4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid) and PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid) are tumour metabolism inhibitors that target adenine nucleotide translocase (ANT) of the inner-mitochondrial membrane. Both compounds are currently being trialled in patients with solid tumours. The trivalent Arsenical moiety of GSAO and PENAO reacts with two matrix facing cysteine residues of ANT, inactivating the transporter. This leads to proliferation arrest and death of tumour and tumour-supporting cells. The two reactive ANT cysteine residues have been identified in this study by expressing cysteine mutants of human ANT1 in Saccharomyces cerevisiae and measuring interaction with the Arsenical moiety of GSAO and PENAO. The Arsenic Atom of both compounds cross-links cysteine residues 57 and 257 of human ANT1. The sulphur Atoms of these two cysteines are 20 A apart in the crystal structures of ANT and the optimal spacing of cysteine thiolates for reaction with As (III) is 3-4 A. This implies that a significant conformational change in ANT is required for the organoArsenicals to react with cysteines 57 and 257. This conformational change may relate to the selectivity of the compounds for proliferating cells.
Liu Xiang - One of the best experts on this subject based on the ideXlab platform.
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Get Phases from Arsenic Anomalous Scattering: de novo SAD Phasing of Two Protein Structures Crystallized in Cacodylate Buffer
plos one, 2011Co-Authors: Liu Xiang, Zhang Heng, Wang Xiao-jun, Li Lan-fen, Su Xiao-dongAbstract:The crystal structures of two proteins, a putative pyrazinamidase/nicotinamidase from the dental pathogen Streptococcus mutans (SmPncA) and the human caspase-6 (Casp6), were solved by de novo Arsenic single-wavelength anomalous diffraction (As-SAD) phasing method. Arsenic (As), an uncommonly used element in SAD phasing, was covalently introduced into proteins by cacodylic acid, the buffering agent in the crystallization reservoirs. In SmPncA, the only cysteine was bound to dimethylarsinoyl, which is a pentavalent Arsenic group (As (V)). This Arsenic Atom and a protein-bound zinc Atom both generated anomalous signals. The predominant contribution, however, was from the As anomalous signals, which were sufficient to phase the SmPncA structure alone. In Casp6, four cysteines were found to bind cacodyl, a trivalent Arsenic group (As (III)), in the presence of the reducing agent, dithiothreitol (DTT), and Arsenic Atoms were the only anomalous scatterers for SAD phasing. Analyses and discussion of these two As-SAD phasing examples and comparison of As with other traditional heavy Atoms that generate anomalous signals, together with a few Arsenic-based de novo phasing cases reported previously strongly suggest that As is an ideal anomalous scatterer for SAD phasing in protein crystallography.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000294686100025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Multidisciplinary SciencesSCI(E)PubMed6ARTICLE9e24227