1a8g: Difference between revisions

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[[Image:1a8g.gif|left|200px]]<br />

[[Image:1a8g.gif|left|200px]]<br /><applet load="1a8g" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="1a8g" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1a8g, resolution 2.50Å" />

'''HIV-1 PROTEASE IN COMPLEX WITH SDZ283-910'''<br />

==Overview==

Based on the X-ray structure of the human immunodeficiency virus type-1, (HIV-1) protease in complex with the statine-derived inhibitor SDZ283-910, a 542 ps molecular dynamics trajectory was computed. For comparison with, the 805 ps trajectory obtained for the uncomplexed enzyme, the theoretical, fluorescence anisotropy decay of the unliganded protease and the inhibitor, complex was calculated from the trajectories of the Trp6A/Trp6B and, Trp42A/Trp42B transition dipole moments. This enabled us to directly, compare the simulated data with the experimental picosecond time-resolved, fluorescence data. Fitting both experimental and simulated data to the, Kohlrausch-Williams-Watts (KWW) function exp(-t/tauk)beta revealed a very, good agreement for the uncomplexed protease as well as for the SDZ283-910, complex. Binding of the inhibitor induced a faster decay of both the, experimental and the computed protease fluorescence anisotropy decay. By, this integrative approach, the atomic detail of inhibitor-induced changes, in the conformational dynamics of the HIV-1 protease was experimentally, verified and will be used for further inhibitor optimisation.

Based on the X-ray structure of the human immunodeficiency virus type-1 (HIV-1) protease in complex with the statine-derived inhibitor SDZ283-910, a 542 ps molecular dynamics trajectory was computed. For comparison with the 805 ps trajectory obtained for the uncomplexed enzyme, the theoretical fluorescence anisotropy decay of the unliganded protease and the inhibitor complex was calculated from the trajectories of the Trp6A/Trp6B and Trp42A/Trp42B transition dipole moments. This enabled us to directly compare the simulated data with the experimental picosecond time-resolved fluorescence data. Fitting both experimental and simulated data to the Kohlrausch-Williams-Watts (KWW) function exp(-t/tauk)beta revealed a very good agreement for the uncomplexed protease as well as for the SDZ283-910 complex. Binding of the inhibitor induced a faster decay of both the experimental and the computed protease fluorescence anisotropy decay. By this integrative approach, the atomic detail of inhibitor-induced changes in the conformational dynamics of the HIV-1 protease was experimentally verified and will be used for further inhibitor optimisation.

==About this Structure==

1A8G is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Active as [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1A8G OCA].

1A8G is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Active as [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A8G OCA].

==Reference==

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[[Category: hydrolase]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on Thu ~~Nov 8 13~~:49:~~15 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:42:02 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1a8g.gif|left|200px]]<br />
+[[Image:1a8g.gif|left|200px]]<br /><applet load="1a8g" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1a8g" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1a8g, resolution 2.50&Aring;" />
 '''HIV-1 PROTEASE IN COMPLEX WITH SDZ283-910'''<br />
 ==Overview==
-Based on the X-ray structure of the human immunodeficiency virus type-1, (HIV-1) protease in complex with the statine-derived inhibitor SDZ283-910, a 542 ps molecular dynamics trajectory was computed. For comparison with, the 805 ps trajectory obtained for the uncomplexed enzyme, the theoretical, fluorescence anisotropy decay of the unliganded protease and the inhibitor, complex was calculated from the trajectories of the Trp6A/Trp6B and, Trp42A/Trp42B transition dipole moments. This enabled us to directly, compare the simulated data with the experimental picosecond time-resolved, fluorescence data. Fitting both experimental and simulated data to the, Kohlrausch-Williams-Watts (KWW) function exp(-t/tauk)beta revealed a very, good agreement for the uncomplexed protease as well as for the SDZ283-910, complex. Binding of the inhibitor induced a faster decay of both the, experimental and the computed protease fluorescence anisotropy decay. By, this integrative approach, the atomic detail of inhibitor-induced changes, in the conformational dynamics of the HIV-1 protease was experimentally, verified and will be used for further inhibitor optimisation.
+Based on the X-ray structure of the human immunodeficiency virus type-1 (HIV-1) protease in complex with the statine-derived inhibitor SDZ283-910, a 542 ps molecular dynamics trajectory was computed. For comparison with the 805 ps trajectory obtained for the uncomplexed enzyme, the theoretical fluorescence anisotropy decay of the unliganded protease and the inhibitor complex was calculated from the trajectories of the Trp6A/Trp6B and Trp42A/Trp42B transition dipole moments. This enabled us to directly compare the simulated data with the experimental picosecond time-resolved fluorescence data. Fitting both experimental and simulated data to the Kohlrausch-Williams-Watts (KWW) function exp(-t/tauk)beta revealed a very good agreement for the uncomplexed protease as well as for the SDZ283-910 complex. Binding of the inhibitor induced a faster decay of both the experimental and the computed protease fluorescence anisotropy decay. By this integrative approach, the atomic detail of inhibitor-induced changes in the conformational dynamics of the HIV-1 protease was experimentally verified and will be used for further inhibitor optimisation.
 ==About this Structure==
-A8G is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Active as [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1A8G OCA].
+A8G is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Active as [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A8G OCA].
 ==Reference==
@@ Line 23: / Line 22: @@
 [[Category: hydrolase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov  8 13:49:15 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:42:02 2008''