3bgb: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older editNewer edit →
No edit summary
No edit summary
Line 1: Line 1:
[[Image:3bgb.png|left|200px]]
==HIV-1 protease in complex with a isobutyl decorated oligoamine==
<StructureSection load='3bgb' size='340' side='right' caption='[[3bgb]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3bgb]] is a 2 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=3BGB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BGB FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=LJG:N,N-(IMINODIETHANE-2,1-DIYL)BIS[4-AMINO-N-(2-METHYLPROPYL)BENZENESULFONAMIDE]'>LJG</scene><br>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bgc|3bgc]]</td></tr>
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1])</td></tr>
<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=3bgb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bgb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bgb RCSB], [http://www.ebi.ac.uk/pdbsum/3bgb 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/bg/3bgb_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 ==
Due to the important role that aspartic proteases play in many patho-physiological processes, they have intensively been targeted by modern drug development. However, up to now, only for two family members, renin and HIV protease, approved drugs are available. Inhibitor development, mostly guided by mimicking the natural peptide substrates, resulted in very potent inhibitors for several targets, but the pharmacokinetic properties of these compounds were often not optimal. Herein we report a novel approach for lead structure discovery of non-peptidic aspartic protease inhibitors using easily accessible achiral linear oligoamines as starting point. An initial library comprising 11 inhibitors was developed and screened against six selected aspartic proteases. Several hits could be identified, among them selective as well as rather promiscuous inhibitors. The design concept was confirmed by determination of the crystal structure of two derivatives in complex with the HIV-1 protease, and represents a promising basis for the further inhibitor development.


{{STRUCTURE_3bgb|  PDB=3bgb  |  SCENE=  }}
Achiral oligoamines as versatile tool for the development of aspartic protease inhibitors.,Blum A, Bottcher J, Sammet B, Luksch T, Heine A, Klebe G, Diederich WE Bioorg Med Chem. 2008 Sep 15;16(18):8574-86. Epub 2008 Aug 7. PMID:18760609<ref>PMID:18760609</ref>


===HIV-1 protease in complex with a isobutyl decorated oligoamine===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
{{ABSTRACT_PUBMED_18760609}}
 
==About this Structure==
[[3bgb]] is a 2 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=3BGB OCA].


==See Also==
==See Also==
*[[Virus protease|Virus protease]]
*[[Virus protease|Virus protease]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:018760609</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 09:14, 29 September 2014

HIV-1 protease in complex with a isobutyl decorated oligoamineHIV-1 protease in complex with a isobutyl decorated oligoamine

Structural highlights

3bgb is a 2 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:,
Related:3bgc
Gene:gag-pol (Human immunodeficiency virus 1)
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

Due to the important role that aspartic proteases play in many patho-physiological processes, they have intensively been targeted by modern drug development. However, up to now, only for two family members, renin and HIV protease, approved drugs are available. Inhibitor development, mostly guided by mimicking the natural peptide substrates, resulted in very potent inhibitors for several targets, but the pharmacokinetic properties of these compounds were often not optimal. Herein we report a novel approach for lead structure discovery of non-peptidic aspartic protease inhibitors using easily accessible achiral linear oligoamines as starting point. An initial library comprising 11 inhibitors was developed and screened against six selected aspartic proteases. Several hits could be identified, among them selective as well as rather promiscuous inhibitors. The design concept was confirmed by determination of the crystal structure of two derivatives in complex with the HIV-1 protease, and represents a promising basis for the further inhibitor development.

Achiral oligoamines as versatile tool for the development of aspartic protease inhibitors.,Blum A, Bottcher J, Sammet B, Luksch T, Heine A, Klebe G, Diederich WE Bioorg Med Chem. 2008 Sep 15;16(18):8574-86. Epub 2008 Aug 7. PMID:18760609[1]

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

See Also

References

  1. ↑ Blum A, Bottcher J, Sammet B, Luksch T, Heine A, Klebe G, Diederich WE. Achiral oligoamines as versatile tool for the development of aspartic protease inhibitors. Bioorg Med Chem. 2008 Sep 15;16(18):8574-86. Epub 2008 Aug 7. PMID:18760609 doi:10.1016/j.bmc.2008.08.012

3bgb, resolution 1.90Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=3bgb&oldid=2003228"