CCL

Összesen 13 találat.
#/oldal:
Részletezés:
Rendezés:

1.

001-es BibID:BIBFORM040632
Első szerző:Bagossi Péter (biokémikus, vegyész)
Cím:Improved parameters for generating partial charges : correlation with observed dipole moments / Péter Bagossi, Gábor Zahuczky, József Tözsér, Irene T. Weber, Robert W. Harrison
Dátum:1999
Megjegyzések:The Universal Force Field was initially combined with the Charge Equilibrium Scheme in the molecular mechanics program AMMP in order to generate partial charges for protein atoms. A new parameter set with improved generation of partial charges has been derived in order to analyse a wider range of atoms and compounds. The electrostatic parameters were modified to achieve better correlation with experimental dipole moments for a training set of 160 compounds, which included alkali metal halogenides, saturated and unsaturated hydrocarbons, alcohols, ethers, amines, thiols, sulphides, oxo compounds, aromatic and heteroaromatic molecules. The correlation coefficient for the calculated and experimental dipole moments was improved from 0.57 to 0.98. The new parameters were tested for another 149 compounds and the correlation coefficient increased from 0.48 to 0.85. The newly generated Modified Parameter Set for AMMP (MOPSA) improves the predictive power of the program, especially in the area of the macromolecular modelling and drug design, where the nonbonded energies play a crucial role.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal of Molecular Modeling. - 5 : 9 (1999), p. 143-152. -
További szerzők:Zahuczky Gábor (1975-) (molekuláris biológus, biokémikus, vegyész) Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész) Weber, Irene T. Harrison, Robert W.
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
Borító:

2.

001-es BibID:BIBFORM040655
Első szerző:Fehér Anita
Cím:Effect of sequence polymorphism and drug resistance on two HIV-1 Gag processing sites / Fehér Anita, Weber Irene T., Bagossi Péter, Boross Péter, Mahalingam Bhuvaneshwari, Louis John M., Copeland Terry D., Torshin Ivan Y., Harrison Robert W., Tözsér József
Dátum:2002
ISSN:0014-2956
Megjegyzések:The HIV-1 proteinase (PR) has proved to be a good target for antiretroviral therapy of AIDS, and various PR inhibitors are now in clinical use. However, there is a rapid selection of viral variants bearing mutations in the proteinase that are resistant to clinical inhibitors. Drug resistance also involves mutations of the nucleocapsid/p1 and p1/p6 cleavage sites of Gag, both in vitro and in vivo. Cleavages at these sites have been shown to be rate limiting steps for polyprotein processing and viral maturation. Furthermore, these sites show significant sequence polymorphism, which also may have an impact on virion infectivity. We have studied the hydrolysis of oligopeptides representing these cleavage sites with representative mutations found as natural variations or that arise as resistant mutations. Wild-type and five drug resistant PRs with mutations within or outside the substrate binding site were tested. While the natural variations showed either increased or decreased susceptibility of peptides toward the proteinases, the resistant mutations always had a beneficial effect on catalytic efficiency. Comparison of the specificity changes obtained for the various substrates suggested that the maximization of the van der Waals contacts between substrate and PR is the major determinant of specificity: the same effect is crucial for inhibitor potency. The natural nucleocapsid/p1 and p1/p6 sites do not appear to be optimized for rapid hydrolysis. Hence, mutation of these rate limiting cleavage sites can partly compensate for the reduced catalytic activity of drug resistant mutant HIV-1 proteinases.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:European Journal Of Biochemistry. - 269 : 16 (2002), p. 4114-4120. -
További szerzők:Weber, Irene T. Bagossi Péter (1966-2011) (biokémikus, vegyész) Boross Péter (1972-) (biokémikus, vegyész) Mahalingam, Bhuvaneshwari Louis, John M. Copeland, Terry D. Torshin, Ivan Y. Harrison, Robert W. Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész)
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

3.

001-es BibID:BIBFORM086386
Első szerző:Liu, Fengling
Cím:Analysis of HIV-1 protease mutants to understand mechanisms of resistance / Liu F., Boross Péter, Tőzsér József, Louis J. M., Harrison R. W., Weber I. T.
Dátum:2005
ISSN:1742-464X
Tárgyszavak:Orvostudományok Klinikai orvostudományok idézhető absztrakt
folyóiratcikk
Megjelenés:Febs Journal. - 272 : Suppl1 (2005), p. 12. -
További szerzők:Boross Péter (1972-) (biokémikus, vegyész) Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész) Louis, John M. Harrison, Robert W. Weber, Irene T.
Pályázati támogatás:OTKA T43482
OTKA
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

4.

001-es BibID:BIBFORM040663
Első szerző:Liu, Fengling
Cím:Kinetic, Stability, and Structural Changes in High-resolution Crystal Structures of HIV-1 Protease with Drug-resistant Mutations L24I, I50V, and G73S / Liu Fengling, Boross Peter I., Wang Yuan-Fang, Tozser Jozsef, Louis John M., Harrison Robert W., Weber Irene T.
Dátum:2005
ISSN:0022-2836
Megjegyzések:The crystal structures, dimer stabilities, and kinetics have been analyzed for wild-type human immunodeficiency virus type 1 (HIV-1) protease (PR) and resistant mutants PR(L24I), PR(I50V), and PR(G73S) to gain insight into the molecular basis of drug resistance. The mutations lie in different structural regions. Mutation I50V alters a residue in the flexible flap that interacts with the inhibitor, L24I alters a residue adjacent to the catalytic Asp25, and G73S lies at the protein surface far from the inhibitor-binding site. PR(L24I) and PR(I50V), showed a 4% and 18% lower k(cat)/K(m), respectively, relative to PR. The relative k(cat)/K(m) of PR(G73S) varied from 14% to 400% when assayed using different substrates. Inhibition constants (K(i)) of the antiviral drug indinavir for the reaction catalyzed by the mutant enzymes were about threefold and 50-fold higher for PR(L24I) and PR(I50V), respectively, relative to PR and PR(G73S). The dimer dissociation constant (K(d)) was estimated to be approximately 20 nM for both PR(L24I) and PR(I50V), and below 5 nM for PR(G73S) and PR. Crystal structures of the mutants PR(L24I), PR(I50V) and PR(G73S) were determined in complexes with indinavir, or the p2/NC substrate analog at resolutions of 1.10-1.50 Angstrom. Each mutant revealed distinct structural changes relative to PR. The mutated residues in PR(L24I) and PR(I50V) had reduced intersubunit contacts, consistent with the increased K(d) for dimer dissociation. Relative to PR, PR(I50V) had fewer interactions of Val50 with inhibitors, in agreement with the dramatically increased K(i). The distal mutation G73S introduced new hydrogen bond interactions that can transmit changes to the substrate-binding site and alter catalytic activity. Therefore, the structural alterations observed for drug-resistant mutations were in agreement with kinetic and stability changes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal Of Molecular Biology. - 354 : 4 (2005), p. 789-800. -
További szerzők:Boross Péter (1972-) (biokémikus, vegyész) Wang, Yuan-Fang Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész) Louis, John M. Harrison, Robert W. Weber, Irene T.
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

5.

001-es BibID:BIBFORM040670
Első szerző:Mahalingam, Bhuvaneshwari
Cím:Combining mutations in HIV-1 protease to understand mechanisms of resistance / Mahalingam Bhuvaneshwari, Boross Peter, Wang Yuan-Fang, Louis John M., Fischer Christopher C., Tozser Jozsef, Harrison Robert W., Weber Irene T.
Dátum:2002
ISSN:0887-3585
Megjegyzések:HIV-1 develops resistance to protease inhibitors predominantly by selecting mutations in the protease gene. Studies of resistant mutants of HIV-1 protease with single amino acid substitutions have shown a range of independent effects on specificity, inhibition, and stability. Four double mutants, K45I/L90M, K45I/V82S, D30N/V82S, and N88D/L90M were selected for analysis on the basis of observations of increased or decreased stability or enzymatic activity for the respective single mutants. The double mutants were assayed for catalysis, inhibition, and stability. Crystal structures were analyzed for the double mutants at resolutions of 2.2-1.2 A to determine the associated molecular changes. Sequence-dependent changes in protease-inhibitor interactions were observed in the crystal structures. Mutations D30N, K45I, and V82S showed altered interactions with inhibitor residues at P2/P2', P3/P3'/P4/P4', and P1/P1', respectively. One of the conformations of Met90 in K45I/L90M has an unfavorably close contact with the carbonyl oxygen of Asp25, as observed previously in the L90M single mutant. The observed catalytic efficiency and inhibition for the double mutants depended on the specific substrate or inhibitor. In particular, large variation in cleavage of p6(pol)-PR substrate was observed, which is likely to result in defects in the maturation of the protease from the Gag-Pol precursor and hence viral replication. Three of the double mutants showed values for stability that were intermediate between the values observed for the respective single mutants. D30N/V82S mutant showed lower stability than either of the two individual mutations, which is possibly due to concerted changes in the central P2-P2' and S2-S2' sites. The complex effects of combining mutations are discussed.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Proteins-Structure Function And Bioinformatics. - 48 : 1 (2002), p. 107-116. -
További szerzők:Boross Péter (1972-) (biokémikus, vegyész) Wang, Yuan-Fang Louis, John M. Fischer, Christopher C. Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész) Harrison, Robert W. Weber, Irene T.
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

6.

001-es BibID:BIBFORM040668
Első szerző:Mahalingam, Bhuvaneshwari
Cím:Crystal structures of HIV protease V82A and L90M mutants reveal changes in the indinavir-binding site / Mahalingam Bhuvaneshwari, Wang Yuan-Fang, Boross Peter I., Tozser Jozsef, Louis John M., Harrison Robert W., Weber Irene T.
Dátum:2004
ISSN:0014-2956
Megjegyzések:The crystal structures of the wild-type HIV-1 protease (PR) and the two resistant variants, PR(V82A) and PR(L90M), have been determined in complex with the antiviral drug, indinavir, to gain insight into the molecular basis of drug resistance. V82A and L90M correspond to an active site mutation and nonactive site mutation, respectively. The inhibition (K(i)) of PR(V82A) and PR(L90M) was 3.3- and 0.16-fold, respectively, relative to the value for PR. They showed only a modest decrease, of 10-15%, in their k(cat)/K(m) values relative to PR. The crystal structures were refined to resolutions of 1.25-1.4 A to reveal critical features associated with inhibitor resistance. PR(V82A) showed local changes in residues 81-82 at the site of the mutation, while PR(L90M) showed local changes near Met90 and an additional interaction with indinavir. These structural differences concur with the kinetic data.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:European Journal Of Biochemistry. - 271 : 8 (2004), p. 1516-1524. -
További szerzők:Wang, Yuan-Fang Boross Péter (1972-) (biokémikus, vegyész) Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész) Louis, John M. Harrison, Robert W. Weber, Irene T.
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

7.

001-es BibID:BIBFORM001484
Első szerző:Sperka Tamás (biokémikus, vegyész, biológia-kémia szakos tanár)
Cím:Bovine leukemia virus protease : comparison with human T-lymphotropic virus and human immunodeficiency virus protease / Sperka T., Miklóssy G., Tie Y., Bagossi P., Zahuczky G., Boross P., Matuz K., Harrison R. W., Weber I., Tőzsér J.
Dátum:2007
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:The Journal of General Virology 88 : 7 (2007), p. 2052-2063. -
További szerzők:Miklóssy Gabriella (1979-) (biológus, vegyész) Tie, Yunfeng Bagossi Péter (1966-2011) (biokémikus, vegyész) Zahuczky Gábor (1975-) (molekuláris biológus, biokémikus, vegyész) Boross Péter (1972-) (biokémikus, vegyész) Matúz Krisztina (1980-) (vegyész, biokémikus) Harrison, Robert W. Weber, Irene T. Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész)
Internet cím:elektronikus változat
DOI
Borító:

8.

001-es BibID:BIBFORM040679
Első szerző:Tie, Yunfeng
Cím:Critical differences in HIV-1 and HIV-2 protease specificity for clinical inhibitors / Tie Yunfeng, Wang Yuan-Fang, Boross Peter I., Chiu Ting-Yi, Ghosh Arun K., Tozser Jozsef, Louis John M., Harrison Robert W., Weber Irene T.
Dátum:2012
ISSN:0961-8368
Megjegyzések:Clinical inhibitor amprenavir (APV) is less effective on HIV-2 protease (PR₂) than on HIV-1 protease (PR₁). We solved the crystal structure of PR₂ with APV at 1.5 Å resolution to identify structural changes associated with the lowered inhibition. Furthermore, we analyzed the PR₁ mutant (PR(1M) ) with substitutions V32I, I47V, and V82I that mimic the inhibitor binding site of PR₂. PR(1M) more closely resembled PR₂ than PR₁ in catalytic efficiency on four substrate peptides and inhibition by APV, whereas few differences were seen for two other substrates and inhibition by saquinavir (SQV) and darunavir (DRV). High resolution crystal structures of PR(1M) with APV, DRV, and SQV were compared with available PR₁ and PR₂ complexes. Val/Ile32 and Ile/Val47 showed compensating interactions with SQV in PR(1M) and PR₁, however, Ile82 interacted with a second SQV bound in an extension of the active site cavity of PR(1M). Residues 32 and 82 maintained similar interactions with DRV and APV in all the enzymes, whereas Val47 and Ile47 had opposing effects in the two subunits. Significantly diminished interactions were seen for the aniline of APV bound in PR₁ (M) and PR₂ relative to the strong hydrogen bonds observed in PR₁, consistent with 15- and 19-fold weaker inhibition, respectively. Overall, PR(1M) partially replicates the specificity of PR₂ and gives insight into drug resistant mutations at residues 32, 47, and 82. Moreover, this analysis provides a structural explanation for the weaker antiviral effects of APV on HIV-2.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Protein Science. - 21 : 3 (2012), p. 339-350. -
További szerzők:Wang, Yuan-Fang Boross Péter (1972-) (biokémikus, vegyész) Chiu, Ting-Yi Ghosh, Arun K. Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész) Louis, John M. Harrison, Robert W. Weber, Irene T.
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

9.

001-es BibID:BIBFORM040678
Első szerző:Tie, Yunfeng
Cím:Molecular basis for substrate recognition and drug resistance from 1.1 to 1.6 A angstroms resolution crystal structures of HIV-1 protease mutants with substrate analogs / Tie Yunfeng, Boross Peter I., Wang Yuan-Fang, Gaddis Laquasha, Liu Fengling, Chen Xianfeng, Tozser Jozsef, Harrison Robert W., Weber Irene T.
Dátum:2005
ISSN:1742-464X
Megjegyzések:HIV-1 protease (PR) and two drug-resistant variants--PR with the V82A mutation (PR(V82A)) and PR with the I84V mutation (PR(I84V))--were studied using reduced peptide analogs of five natural cleavage sites (CA-p2, p2-NC, p6pol-PR, p1-p6 and NC-p1) to understand the structural and kinetic changes. The common drug-resistant mutations V82A and I84V alter residues forming the substrate-binding site. Eight crystal structures were refined at resolutions of 1.10-1.60 A. Differences in the PR-analog interactions depended on the peptide sequence and were consistent with the relative inhibition. Analog p6(pol)-PR formed more hydrogen bonds of P2 Asn with PR and fewer van der Waals contacts at P1' Pro compared with those formed by CA-p2 or p2-NC in PR complexes. The P3 Gly in p1-p6 provided fewer van der Waals contacts and hydrogen bonds at P2-P3 and more water-mediated interactions. PR(I84V) showed reduced van der Waals interactions with inhibitor compared with PR, which was consistent with kinetic data. The structures suggest that the binding affinity for mutants is modulated by the conformational flexibility of the substrate analogs. The complexes of PR(V82A) showed smaller shifts of the main chain atoms of Ala82 relative to PR, but more movement of the peptide analog, compared to complexes with clinical inhibitors. PR(V82A) was able to compensate for the loss of interaction with inhibitor caused by mutation, in agreement with kinetic data, but substrate analogs have more flexibility than the drugs to accommodate the structural changes caused by mutation. Hence, these structures help to explain how HIV can develop drug resistance while retaining the ability of PR to hydrolyze natural substrates.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Febs Journal. - 272 : 20 (2005), p. 5265-5277. -
További szerzők:Boross Péter (1972-) (biokémikus, vegyész) Wang, Yuan-Fang Gaddis, Laquasha Liu, Fengling Chen, Xianfeng Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész) Harrison, Robert W. Weber, Irene T.
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

10.

001-es BibID:BIBFORM001504
Első szerző:Tie, Yunfeng
Cím:Atomic resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavir / Tie Y., Kovalevsky A. Y., Boross P., Wang Y. F., Ghosh A. K., Tozser J., Harrison R. W., Weber I. T.
Dátum:2007
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Proteins 67 : 1 (2007), p. 232-242. -
További szerzők:Kovalevsky, Andrey Yu Boross Péter (1972-) (biokémikus, vegyész) Wang, Yuan-Fang Ghosh, Arun K. Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész) Harrison, Robert W. Weber, Irene T.
Internet cím:elektronikus változat
DOI
Borító:

11.

001-es BibID:BIBFORM040689
Első szerző:Tőzsér József (molekuláris biológus, biokémikus, vegyész)
Cím:Activity of Tethered Human Immunodeficiency Virus 1 Protease Containing Mutations in the Flap Region of One Subunit / Tozser Jozsef, Yin Fay H., Cheng Yin-Shyun E., Bagossi Peter, Weber Irene T., Harrison Robert W., Oroszlan Stephen
Dátum:1997
ISSN:0014-2956
Megjegyzések:The tethered-dimer protease of human immunodeficiency virus 1 (HIV-1) [Cheng Y.-S. E., Yin, F.H., Foundling, S., Blomstrom, D. & Kettner, C. A. (1990) Proc. Natl Acad. Sci. USA 87, 9660-9664] and its mutants containing amino acid substitutions or deletions or both in only one flap region were expressed in Escherichia coli. These mutant enzymes showed various degrees of self-processing and significantly reduced catalytic activity toward oligopeptide substrates compared with the wild type. Kinetic parameters determined for one of the oligopeptide substrates showed a dramatic increase in K(m) and decrease in Kcat values. Unexpectedly, the substrate cleavage was more efficient in low salt concentration for a mutant containing a shortened hydrophilic flap. Assays with oligopeptides representing naturally occurring cleavage sites or oligopeptides containing single amino acid substitutions at the P2 and P2' substrate positions showed only moderate changes in the substrate specificity of the mutant proteases. Predicted structures for the mutants were constructed by molecular modeling and used to interpret the results of kinetic measurements. In general, the data suggest that the mutated part of the flaps does not have a major role in determining substrate specificity; rather, it provides the hydrophobic environment and hydrogen-bond interactions with the conserved water that are necessary for efficient substrate binding and catalysis.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:European Journal Of Biochemistry 244 : 1 (1997), p. 235-241. -
További szerzők:Yin, Fay H. Cheng, Yin-Shyun E. Bagossi Péter (1966-2011) (biokémikus, vegyész) Weber, Irene T. Harrison, Robert W. Oroszlan, Stephen
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

12.

001-es BibID:BIBFORM040126
Első szerző:Tőzsér József (molekuláris biológus, biokémikus, vegyész)
Cím:Comparison of the substrate specificity of the human T-cell leukemia virus and human immunodeficiency virus proteinases / József Tőzsér, Gábor Zahuczky, Péter Bagossi, John M. Louis, Terry D. Copeland, Stephen Oroszlan, Robert W. Harrison, Irene T. Weber
Dátum:2000
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:European Journal of Biochemistry. - 267 : 20 (2000), p. 6287-6295. -
További szerzők:Zahuczky Gábor (1975-) (molekuláris biológus, biokémikus, vegyész) Bagossi Péter (1966-2011) (biokémikus, vegyész) Louis, John M. Copeland, Terry D. Oroszlan, Stephen Harrison, Robert W. Weber, Irene T.
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
Szerző által megadott URL 856 41
DOI
Borító:
Rekordok letöltése1 2