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2p3d

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Revision as of 07:47, 31 July 2019

Crystal Structure of the multi-drug resistant mutant subtype F HIV protease complexed with TL-3 inhibitor

Structural highlights

2p3d is a 2 chain structure with sequence from 9hiv1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2p3a, 2p3b, 2p3c
Activity:	HIV-1 retropepsin, with EC number 3.4.23.16
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Although a majority of HIV-1 infections in Brazil are caused by the subtype B virus (also prevalent in the United States and Western Europe), viral subtypes F and C are also found very frequently. Genomic differences between the subtypes give rise to sequence variations in the encoded proteins, including the HIV-1 protease. The current anti-HIV drugs have been developed primarily against subtype B and the effects arising from the combination of drug-resistance mutations with the naturally existing polymorphisms in non-B HIV-1 subtypes are only beginning to be elucidated. To gain more insights into the structure and function of different variants of HIV proteases, we have determined a 2.1 A structure of the native subtype F HIV-1 protease (PR) in complex with the protease inhibitor TL-3. We have also solved crystal structures of two multi-drug resistant mutant HIV PRs in complex with TL-3, from subtype B (Bmut) carrying the primary mutations V82A and L90M, and from subtype F (Fmut) carrying the primary mutation V82A plus the secondary mutation M36I, at 1.75 A and 2.8 A resolution, respectively. The proteases Bmut, Fwt and Fmut exhibit sevenfold, threefold, and 54-fold resistance to TL-3, respectively. In addition, the structure of subtype B wild type HIV-PR in complex with TL-3 has been redetermined in space group P6(1), consistent with the other three structures. Our results show that the primary mutation V82A causes the known effect of collapsing the S1/S1' pockets that ultimately lead to the reduced inhibitory effect of TL-3. Our results further indicate that two naturally occurring polymorphic substitutions in subtype F and other non-B HIV proteases, M36I and L89M, may lead to early development of drug resistance in patients infected with non-B HIV subtypes.

Structural characterization of B and non-B subtypes of HIV-protease: insights into the natural susceptibility to drug resistance development.,Sanches M, Krauchenco S, Martins NH, Gustchina A, Wlodawer A, Polikarpov I J Mol Biol. 2007 Jun 15;369(4):1029-40. Epub 2007 Mar 24. PMID:17467738^[1]

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

References

↑ Sanches M, Krauchenco S, Martins NH, Gustchina A, Wlodawer A, Polikarpov I. Structural characterization of B and non-B subtypes of HIV-protease: insights into the natural susceptibility to drug resistance development. J Mol Biol. 2007 Jun 15;369(4):1029-40. Epub 2007 Mar 24. PMID:17467738 doi:10.1016/j.jmb.2007.03.049

1 Structural highlights
2 Evolutionary Conservation
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2p3d"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the multi-drug resistant mutant subtype F HIV protease complexed with TL-3 inhibitor==
-<StructureSection load='2p3d' size='340' side='right' caption='[[2p3d]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+<StructureSection load='2p3d' size='340' side='right'caption='[[2p3d]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2p3d]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P3D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2P3D FirstGlance]. <br>
@@ Line 13: / Line 13: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p3/2p3d_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p3/2p3d_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 30: / Line 30: @@
 ==See Also==
-*[[Immunodeficiency virus protease|Immunodeficiency virus protease]]
+*[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]]
 == References ==
 <references/>
@@ Line 36: / Line 36: @@
 </StructureSection>
 [[Category: HIV-1 retropepsin]]
+[[Category: Large Structures]]
 [[Category: Gustchina, A]]
 [[Category: Krauchenco, S]]

2p3d

From Proteopedia

Revision as of 07:47, 31 July 2019

Crystal Structure of the multi-drug resistant mutant subtype F HIV protease complexed with TL-3 inhibitor

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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