1a94: Difference between revisions

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[[Image:1a94.png|left|200px]]
==STRUCTURAL BASIS FOR SPECIFICITY OF RETROVIRAL PROTEASES==
<StructureSection load='1a94' size='340' side='right' caption='[[1a94]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1a94]] is a 4 chain structure with sequence from [http://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=1A94 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1A94 FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0Q4:N-[(2R)-2-({N~5~-[AMINO(IMINIO)METHYL]-L-ORNITHYL-L-VALYL}AMINO)-4-METHYLPENTYL]-L-PHENYLALANYL-L-ALPHA-GLUTAMYL-L-ALANYL-L-NORLEUCINAMIDE'>0Q4</scene><br>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1a94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a94 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1a94 RCSB], [http://www.ebi.ac.uk/pdbsum/1a94 PDBsum]</span></td></tr>
<table>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a9/1a94_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Rous sarcoma virus (RSV) protease S9 variant has been engineered to exhibit high affinity for HIV-1 protease substrates and inhibitors in order to verify the residues deduced to be critical for the specificity differences. The variant has 9 substitutions (S38T, I42D, I44V, M73V, A100L, V104T, R105P, G106V, and S107N) of structurally equivalent residues from HIV-1 protease. Unlike the wild-type enzyme, RSV S9 protease hydrolyzes peptides representing the HIV-1 protease polyprotein cleavage sites. The crystal structure of RSV S9 protease with the inhibitor, Arg-Val-Leu-r-Phe-Glu-Ala-Nle-NH2, a reduced peptide analogue of the HIV-1 CA-p2 cleavage site, has been refined to an R factor of 0.175 at 2.4-A resolution. The structure shows flap residues that were not visible in the previous crystal structure of unliganded wild-type enzyme. Flap residues 64-76 are structurally similar to residues 47-59 of HIV-1 protease. However, residues 61-63 form unique loops at the base of the flaps. Mutational analysis indicates that these loop residues are essential for catalytic activity. Side chains of flap residues His 65 and Gln 63' make hydrogen bond interactions with the inhibitor P3 amide and P4' carbonyl oxygen, respectively. Other interactions of RSV S9 protease with the CA-p2 analogue are very similar to those observed in the crystal structure of HIV-1 protease with the same inhibitor. This is the first crystal structure of an avian retroviral protease in complex with an inhibitor, and it verifies our knowledge of the molecular basis for specificity differences between RSV and HIV-1 proteases.


{{STRUCTURE_1a94|  PDB=1a94  |  SCENE=  }}
Structural basis for specificity of retroviral proteases.,Wu J, Adomat JM, Ridky TW, Louis JM, Leis J, Harrison RW, Weber IT Biochemistry. 1998 Mar 31;37(13):4518-26. PMID:9521772<ref>PMID:9521772</ref>


===STRUCTURAL BASIS FOR SPECIFICITY OF RETROVIRAL PROTEASES===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
{{ABSTRACT_PUBMED_9521772}}
 
==About this Structure==
[[1a94]] is a 4 chain structure with sequence from [http://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=1A94 OCA].


==See Also==
==See Also==
*[[Virus protease|Virus protease]]
*[[Virus protease|Virus protease]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:009521772</ref><references group="xtra"/>
__TOC__
</StructureSection>
[[Category: HIV-1 retropepsin]]
[[Category: HIV-1 retropepsin]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Human immunodeficiency virus 1]]

Revision as of 11:35, 23 July 2014

STRUCTURAL BASIS FOR SPECIFICITY OF RETROVIRAL PROTEASESSTRUCTURAL BASIS FOR SPECIFICITY OF RETROVIRAL PROTEASES

Structural highlights

1a94 is a 4 chain structure with sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:HIV-1 retropepsin, with EC number 3.4.23.16
Resources:FirstGlance, OCA, RCSB, PDBsum

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

The Rous sarcoma virus (RSV) protease S9 variant has been engineered to exhibit high affinity for HIV-1 protease substrates and inhibitors in order to verify the residues deduced to be critical for the specificity differences. The variant has 9 substitutions (S38T, I42D, I44V, M73V, A100L, V104T, R105P, G106V, and S107N) of structurally equivalent residues from HIV-1 protease. Unlike the wild-type enzyme, RSV S9 protease hydrolyzes peptides representing the HIV-1 protease polyprotein cleavage sites. The crystal structure of RSV S9 protease with the inhibitor, Arg-Val-Leu-r-Phe-Glu-Ala-Nle-NH2, a reduced peptide analogue of the HIV-1 CA-p2 cleavage site, has been refined to an R factor of 0.175 at 2.4-A resolution. The structure shows flap residues that were not visible in the previous crystal structure of unliganded wild-type enzyme. Flap residues 64-76 are structurally similar to residues 47-59 of HIV-1 protease. However, residues 61-63 form unique loops at the base of the flaps. Mutational analysis indicates that these loop residues are essential for catalytic activity. Side chains of flap residues His 65 and Gln 63' make hydrogen bond interactions with the inhibitor P3 amide and P4' carbonyl oxygen, respectively. Other interactions of RSV S9 protease with the CA-p2 analogue are very similar to those observed in the crystal structure of HIV-1 protease with the same inhibitor. This is the first crystal structure of an avian retroviral protease in complex with an inhibitor, and it verifies our knowledge of the molecular basis for specificity differences between RSV and HIV-1 proteases.

Structural basis for specificity of retroviral proteases.,Wu J, Adomat JM, Ridky TW, Louis JM, Leis J, Harrison RW, Weber IT Biochemistry. 1998 Mar 31;37(13):4518-26. PMID:9521772[1]

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

See Also

References

  1. Wu J, Adomat JM, Ridky TW, Louis JM, Leis J, Harrison RW, Weber IT. Structural basis for specificity of retroviral proteases. Biochemistry. 1998 Mar 31;37(13):4518-26. PMID:9521772 doi:10.1021/bi972183g

1a94, resolution 2.00Å

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