7myp: Difference between revisions

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~~'''Unreleased structure'''~~

~~The entry~~ 7myp is ~~ON HOLD~~

==Crystal Structure of HIV-1 PRS17 with GRL-44-10A==

== Structural highlights ==

<table><tr><td colspan='2'>[[7myp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MYP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MYP FirstGlance]. <br>

</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=G04:(3R,3AS,4R,6AR)-4-METHOXYHEXAHYDROFURO[2,3-B]FURAN-3-YL+[(2S,3R)-3-HYDROXY-4-{[(4-METHOXYPHENYL)SULFONYL](2-METHYLPROPYL)AMINO}-1-PHENYLBUTAN-2-YL]CARBAMATE'>G04</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7myp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7myp OCA], [https://pdbe.org/7myp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7myp RCSB], [https://www.ebi.ac.uk/pdbsum/7myp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7myp ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/I7BFC3_9HIV1 I7BFC3_9HIV1]

== Publication Abstract from PubMed ==

The emergence of multidrug resistant (MDR) HIV strains severely reduces the effectiveness of antiretroviral therapy. Clinical inhibitor darunavir (1) has picomolar binding affinity for HIV-1 protease (PR), however, drug resistant variants like PR(S17) show poor inhibition by 1, despite the presence of only two mutated residues in the inhibitor-binding site. Antiviral inhibitors that target MDR proteases like PR(S17) would be valuable as therapeutic agents. Inhibitors 2 and 3 derived from 1 through substitutions at P1, P2 and P2' positions exhibit 3.4- to 500-fold better inhibition than clinical inhibitors for PR(S17) with the exception of amprenavir. Crystal structures of PR(S17)/2 and PR(S17)/3 reveal how these inhibitors target the two active site mutations of PR(S17). The substituted methoxy P2 group of 2 forms new interactions with G48V mutation, while the modified bis-fluoro-benzyl P1 group of 3 forms a halogen interaction with V82S mutation, contributing to improved inhibition of PR(S17).

~~Authors:~~ Agniswamy, J., Weber, I.T.

Novel HIV PR inhibitors with C4-substituted bis-THF and bis-fluoro-benzyl target the two active site mutations of highly drug resistant mutant PR(S17).,Agniswamy J, Kneller DW, Ghosh AK, Weber IT Biochem Biophys Res Commun. 2021 Aug 20;566:30-35. doi:, 10.1016/j.bbrc.2021.05.094. Epub 2021 Jun 7. PMID:34111669<ref>PMID:34111669</ref>

~~Description: Crystal Structure~~ of ~~HIV~~-1 ~~PRS17 with GRL-44-10A~~

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

[[Category: Agniswamy, J]]

[[Category: Weber~~, I.T~~]]

== References ==

__TOC__

</StructureSection>

[[Category: Human immunodeficiency virus 1]]

[[Category: Large Structures]]

[[Category: Agniswamy J]]

[[Category: Weber IT]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 7myp is ON HOLD
+==Crystal Structure of HIV-1 PRS17 with GRL-44-10A==
+<StructureSection load='7myp' size='340' side='right'caption='[[7myp]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7myp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MYP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MYP FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=G04:(3R,3AS,4R,6AR)-4-METHOXYHEXAHYDROFURO[2,3-B]FURAN-3-YL+[(2S,3R)-3-HYDROXY-4-{[(4-METHOXYPHENYL)SULFONYL](2-METHYLPROPYL)AMINO}-1-PHENYLBUTAN-2-YL]CARBAMATE'>G04</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7myp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7myp OCA], [https://pdbe.org/7myp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7myp RCSB], [https://www.ebi.ac.uk/pdbsum/7myp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7myp ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/I7BFC3_9HIV1 I7BFC3_9HIV1]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The emergence of multidrug resistant (MDR) HIV strains severely reduces the effectiveness of antiretroviral therapy. Clinical inhibitor darunavir (1) has picomolar binding affinity for HIV-1 protease (PR), however, drug resistant variants like PR(S17) show poor inhibition by 1, despite the presence of only two mutated residues in the inhibitor-binding site. Antiviral inhibitors that target MDR proteases like PR(S17) would be valuable as therapeutic agents. Inhibitors 2 and 3 derived from 1 through substitutions at P1, P2 and P2' positions exhibit 3.4- to 500-fold better inhibition than clinical inhibitors for PR(S17) with the exception of amprenavir. Crystal structures of PR(S17)/2 and PR(S17)/3 reveal how these inhibitors target the two active site mutations of PR(S17). The substituted methoxy P2 group of 2 forms new interactions with G48V mutation, while the modified bis-fluoro-benzyl P1 group of 3 forms a halogen interaction with V82S mutation, contributing to improved inhibition of PR(S17).
-Authors: Agniswamy, J., Weber, I.T.
+Novel HIV PR inhibitors with C4-substituted bis-THF and bis-fluoro-benzyl target the two active site mutations of highly drug resistant mutant PR(S17).,Agniswamy J, Kneller DW, Ghosh AK, Weber IT Biochem Biophys Res Commun. 2021 Aug 20;566:30-35. doi:, 10.1016/j.bbrc.2021.05.094. Epub 2021 Jun 7. PMID:34111669<ref>PMID:34111669</ref>
-Description: Crystal Structure of HIV-1 PRS17 with GRL-44-10A
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Agniswamy, J]]
+<div class="pdbe-citations 7myp" style="background-color:#fffaf0;"></div>
-[[Category: Weber, I.T]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Human immunodeficiency virus 1]]
+[[Category: Large Structures]]
+[[Category: Agniswamy J]]
+[[Category: Weber IT]]