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2pxr

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[[Image:2pxr.jpg|left|200px]]<br /><applet load="2pxr" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2pxr, resolution 1.500&Aring;" />
 
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'''Crystal Structure of HIV-1 CA146 in the Presence of CAP-1'''<br />
 
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==Overview==
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==Crystal Structure of HIV-1 CA146 in the Presence of CAP-1==
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The CA domain of the human immunodeficiency virus type 1 (HIV-1) Gag polyprotein plays critical roles in both the early and late phases of viral replication and is therefore an attractive antiviral target. Compounds with antiviral activity were recently identified that bind to the N-terminal domain of CA (CA N) and inhibit capsid assembly during viral maturation. We have determined the structure of the complex between CA N and the antiviral assembly inhibitor N-(3-chloro-4-methylphenyl)-N'-{2-[({5-[(dimethylamino)-methyl]-2-furyl}-m ethyl)-sulfanyl]ethyl}-urea) (CAP-1) using a combination of NMR spectroscopy and X-ray crystallography. The protein undergoes a remarkable conformational change upon CAP-1 binding, in which Phe32 is displaced from its buried position in the protein core to open a deep hydrophobic cavity that serves as the ligand binding site. The aromatic ring of CAP-1 inserts into the cavity, with the urea NH groups forming hydrogen bonds with the backbone oxygen of Val59 and the dimethylamonium group interacting with the side-chains of Glu28 and Glu29. Elements that could be exploited to improve binding affinity are apparent in the structure. The displacement of Phe32 by CAP-1 appears to be facilitated by a strained main-chain conformation, which suggests a potential role for a Phe32 conformational switch during normal capsid assembly.
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<StructureSection load='2pxr' size='340' side='right'caption='[[2pxr]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[2pxr]] is a 1 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=2PXR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PXR FirstGlance]. <br>
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2PXR 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] with <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PXR OCA].
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
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<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=ZN:ZINC+ION'>ZN</scene></td></tr>
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==Reference==
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2pxr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pxr OCA], [https://pdbe.org/2pxr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pxr RCSB], [https://www.ebi.ac.uk/pdbsum/2pxr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pxr ProSAT]</span></td></tr>
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Structure of the antiviral assembly inhibitor CAP-1 complex with the HIV-1 CA protein., Kelly BN, Kyere S, Kinde I, Tang C, Howard BR, Robinson H, Sundquist WI, Summers MF, Hill CP, J Mol Biol. 2007 Oct 19;373(2):355-66. Epub 2007 Aug 15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17826792 17826792]
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q79791_9HIV1 Q79791_9HIV1] Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex (By similarity).[SAAS:SAAS000071_004_008806] Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers (By similarity).[SAAS:SAAS000071_004_011858]
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__TOC__
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</StructureSection>
[[Category: Human immunodeficiency virus 1]]
[[Category: Human immunodeficiency virus 1]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Kelly, B N.]]
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[[Category: Kelly BN]]
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[[Category: CL]]
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[[Category: ZN]]
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[[Category: anti-viral]]
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[[Category: hiv-1]]
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[[Category: small molecule inhibition]]
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[[Category: viral capsid]]
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[[Category: viral protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:34:03 2008''
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Current revision

Crystal Structure of HIV-1 CA146 in the Presence of CAP-1

PDB ID 2pxr

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