1s6p: Difference between revisions

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[[Image:1s6p.gif|left|200px]]<br />

[[Image:1s6p.gif|left|200px]]<br /><applet load="1s6p" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="1s6p" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1s6p, resolution 2.90Å" />

'''CRYSTAL STRUCTURE OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 REVERSE TRANSCRIPTASE (RT) IN COMPLEX WITH JANSSEN-R100943'''<br />

==Overview==

Anti-AIDS drug candidate and non-nucleoside reverse transcriptase, inhibitor (NNRTI) TMC125-R165335 (etravirine) caused an initial drop in, viral load similar to that observed with a five-drug combination in naive, patients and retains potency in patients infected with NNRTI-resistant, HIV-1 variants. TMC125-R165335 and related anti-AIDS drug candidates can, bind the enzyme RT in multiple conformations and thereby escape the, effects of drug-resistance mutations. Structural studies showed that this, inhibitor and other diarylpyrimidine (DAPY) analogues can adapt to changes, in the NNRTI-binding pocket in several ways: (1). DAPY analogues can bind, in at least two conformationally distinct modes; (2). within a given, binding mode, torsional flexibility ("wiggling") of DAPY analogues permits, access to numerous conformational variants; and (3). the compact design of, the DAPY analogues permits significant repositioning and reorientation, (translation and rotation) within the pocket ("jiggling"). Such, adaptations appear to be critical for potency against wild-type and a wide, range of drug-resistant mutant HIV-1 RTs. Exploitation of favorable, components of inhibitor conformational flexibility (such as torsional, flexibility about strategically located chemical bonds) can be a powerful, drug design concept, especially for designing drugs that will be effective, against rapidly mutating targets.

Anti-AIDS drug candidate and non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC125-R165335 (etravirine) caused an initial drop in viral load similar to that observed with a five-drug combination in naive patients and retains potency in patients infected with NNRTI-resistant HIV-1 variants. TMC125-R165335 and related anti-AIDS drug candidates can bind the enzyme RT in multiple conformations and thereby escape the effects of drug-resistance mutations. Structural studies showed that this inhibitor and other diarylpyrimidine (DAPY) analogues can adapt to changes in the NNRTI-binding pocket in several ways: (1). DAPY analogues can bind in at least two conformationally distinct modes; (2). within a given binding mode, torsional flexibility ("wiggling") of DAPY analogues permits access to numerous conformational variants; and (3). the compact design of the DAPY analogues permits significant repositioning and reorientation (translation and rotation) within the pocket ("jiggling"). Such adaptations appear to be critical for potency against wild-type and a wide range of drug-resistant mutant HIV-1 RTs. Exploitation of favorable components of inhibitor conformational flexibility (such as torsional flexibility about strategically located chemical bonds) can be a powerful drug design concept, especially for designing drugs that will be effective against rapidly mutating targets.

==About this Structure==

1S6P is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with MG and IET as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1S6P OCA].

1S6P is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=IET:'>IET</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S6P OCA].

==Reference==

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[[Category: reverse transcriptase]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on Thu ~~Nov 8~~ 14:27:~~56 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:58:35 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1s6p.gif|left|200px]]<br />
+[[Image:1s6p.gif|left|200px]]<br /><applet load="1s6p" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1s6p" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1s6p, resolution 2.90&Aring;" />
 '''CRYSTAL STRUCTURE OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 REVERSE TRANSCRIPTASE (RT) IN COMPLEX WITH JANSSEN-R100943'''<br />
 ==Overview==
-Anti-AIDS drug candidate and non-nucleoside reverse transcriptase, inhibitor (NNRTI) TMC125-R165335 (etravirine) caused an initial drop in, viral load similar to that observed with a five-drug combination in naive, patients and retains potency in patients infected with NNRTI-resistant, HIV-1 variants. TMC125-R165335 and related anti-AIDS drug candidates can, bind the enzyme RT in multiple conformations and thereby escape the, effects of drug-resistance mutations. Structural studies showed that this, inhibitor and other diarylpyrimidine (DAPY) analogues can adapt to changes, in the NNRTI-binding pocket in several ways: (1). DAPY analogues can bind, in at least two conformationally distinct modes; (2). within a given, binding mode, torsional flexibility ("wiggling") of DAPY analogues permits, access to numerous conformational variants; and (3). the compact design of, the DAPY analogues permits significant repositioning and reorientation, (translation and rotation) within the pocket ("jiggling"). Such, adaptations appear to be critical for potency against wild-type and a wide, range of drug-resistant mutant HIV-1 RTs. Exploitation of favorable, components of inhibitor conformational flexibility (such as torsional, flexibility about strategically located chemical bonds) can be a powerful, drug design concept, especially for designing drugs that will be effective, against rapidly mutating targets.
+Anti-AIDS drug candidate and non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC125-R165335 (etravirine) caused an initial drop in viral load similar to that observed with a five-drug combination in naive patients and retains potency in patients infected with NNRTI-resistant HIV-1 variants. TMC125-R165335 and related anti-AIDS drug candidates can bind the enzyme RT in multiple conformations and thereby escape the effects of drug-resistance mutations. Structural studies showed that this inhibitor and other diarylpyrimidine (DAPY) analogues can adapt to changes in the NNRTI-binding pocket in several ways: (1). DAPY analogues can bind in at least two conformationally distinct modes; (2). within a given binding mode, torsional flexibility ("wiggling") of DAPY analogues permits access to numerous conformational variants; and (3). the compact design of the DAPY analogues permits significant repositioning and reorientation (translation and rotation) within the pocket ("jiggling"). Such adaptations appear to be critical for potency against wild-type and a wide range of drug-resistant mutant HIV-1 RTs. Exploitation of favorable components of inhibitor conformational flexibility (such as torsional flexibility about strategically located chemical bonds) can be a powerful drug design concept, especially for designing drugs that will be effective against rapidly mutating targets.
 ==About this Structure==
-S6P is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with MG and IET as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1S6P OCA].
+S6P is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=IET:'>IET</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S6P OCA].
 ==Reference==
@@ Line 27: / Line 26: @@
 [[Category: reverse transcriptase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov  8 14:27:56 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:58:35 2008''