1sbg: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older editNewer edit →
m Protected "1sbg" [edit=sysop:move=sysop]
No edit summary
Line 1: Line 1:
{{Seed}}
<table cellpadding='5'><tr><td style='background-color: yellow;border:2px solid black;font-size:150%;'>
{{Template:Possible_fraud}}
WARNING: This structure was flagged as problematic. For additional information see '''2009, December:''' at [[Retractions and Fraud]].</td></tr></table>
[[Image:1sbg.png|left|200px]]
==AN ORALLY-BIOAVAILABLE HIV-1 PROTEASE INHIBITOR CONTAINING AN IMIDAZOLE-DERIVED PEPTIDE BOND REPLACEMENT. CRYSTALLOGRAPHIC AND PHARMACOKINETIC ANALYSIS==
<StructureSection load='1sbg' size='340' side='right' caption='[[1sbg]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1sbg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_type_1_bh10 Human immunodeficiency virus type 1 bh10]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SBG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1SBG FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IM1:(2R,4S,5S,1S)-2-PHENYLMETHYL-4-HYDROXY-5-(TERT-BUTOXYCARBONYL)AMINO-6-PHENYL+HEXANOYL-N-(1-IMIDAZO-2-YL)-2-METHYLPROPANAMIDE'>IM1</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1sbg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sbg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1sbg RCSB], [http://www.ebi.ac.uk/pdbsum/1sbg 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/sb/1sbg_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 ==
(2R,4S,5S,1'S)-2-Phenylmethyl-4-hydroxy-5-(tert-butoxycarbonyl) amino-6-phenylhexanoyl-N-(1'-imidazo-2-yl)-2'-methylpropanamide (compound 2) is a tripeptide analogue inhibitor of HIV-1 protease in which a C-terminal imidazole substituent constitutes an isoelectronic, structural mimic of a carboxamide group. Compound 2 is a potent inhibitor of the protease (K(i) = 18 nM) and inhibits HIV-1 acute infectivity of CD4+ T-lymphocytes (IC50 = 570 nM). Crystallographic analysis of an HIV-1 protease-compound 2 complex demonstrates that the nitrogen atoms of the imidazole ring assume the same hydrogen-bonding interactions with the protease as amide linkages in other peptide analogue inhibitors. The sole substitution of the C-terminal carboxamide of a hydroxyethylene-containing tripeptide analogue with an imidazole group imparts greatly improved pharmacokinetic and oral bioavailability properties on the compound compared to its carboxamide-containing homologue (compound 1). While the oral bioavailability of compound 1 in rats was negligible, compound 2 displayed oral bioavailabilities of 30% and 14%, respectively, in rats and monkeys.


<!--
An orally bioavailable HIV-1 protease inhibitor containing an imidazole-derived peptide bond replacement: crystallographic and pharmacokinetic analysis.,Abdel-Meguid SS, Metcalf BW, Carr TJ, Demarsh P, DesJarlais RL, Fisher S, Green DW, Ivanoff L, Lambert DM, Murthy KH, et al. Biochemistry. 1994 Oct 4;33(39):11671-7. PMID:7918383<ref>PMID:7918383</ref>
The line below this paragraph, containing "STRUCTURE_1sbg", creates the "Structure Box" on the page.
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
or leave the SCENE parameter empty for the default display.
-->
{{STRUCTURE_1sbg|  PDB=1sbg  |  SCENE=  }}


===AN ORALLY-BIOAVAILABLE HIV-1 PROTEASE INHIBITOR CONTAINING AN IMIDAZOLE-DERIVED PEPTIDE BOND REPLACEMENT. CRYSTALLOGRAPHIC AND PHARMACOKINETIC ANALYSIS===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


 
==See Also==
<!--
*[[Retractions and Fraud|Retractions and Fraud]]
The line below this paragraph, {{ABSTRACT_PUBMED_7918383}}, adds the Publication Abstract to the page
== References ==
(as it appears on PubMed at http://www.pubmed.gov), where 7918383 is the PubMed ID number.
<references/>
-->
__TOC__
{{ABSTRACT_PUBMED_7918383}}
</StructureSection>
 
[[Category: Human immunodeficiency virus type 1 bh10]]
==About this Structure==
[[Category: Abdel-Meguid, S]]
1SBG is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_type_1_(isolate_bh10) Human immunodeficiency virus type 1 (isolate bh10)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SBG OCA].
[[Category: Zhao, B]]
 
==Reference==
<ref group="xtra">PMID:7918383</ref><references group="xtra"/>
[[Category: Abdel-Meguid, S.]]
[[Category: Zhao, B.]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 09:30:18 2009''

Revision as of 11:29, 18 November 2014

WARNING: This structure was flagged as problematic. For additional information see 2009, December: at Retractions and Fraud.

AN ORALLY-BIOAVAILABLE HIV-1 PROTEASE INHIBITOR CONTAINING AN IMIDAZOLE-DERIVED PEPTIDE BOND REPLACEMENT. CRYSTALLOGRAPHIC AND PHARMACOKINETIC ANALYSISAN ORALLY-BIOAVAILABLE HIV-1 PROTEASE INHIBITOR CONTAINING AN IMIDAZOLE-DERIVED PEPTIDE BOND REPLACEMENT. CRYSTALLOGRAPHIC AND PHARMACOKINETIC ANALYSIS

Structural highlights

1sbg is a 2 chain structure with sequence from Human immunodeficiency virus type 1 bh10. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
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

(2R,4S,5S,1'S)-2-Phenylmethyl-4-hydroxy-5-(tert-butoxycarbonyl) amino-6-phenylhexanoyl-N-(1'-imidazo-2-yl)-2'-methylpropanamide (compound 2) is a tripeptide analogue inhibitor of HIV-1 protease in which a C-terminal imidazole substituent constitutes an isoelectronic, structural mimic of a carboxamide group. Compound 2 is a potent inhibitor of the protease (K(i) = 18 nM) and inhibits HIV-1 acute infectivity of CD4+ T-lymphocytes (IC50 = 570 nM). Crystallographic analysis of an HIV-1 protease-compound 2 complex demonstrates that the nitrogen atoms of the imidazole ring assume the same hydrogen-bonding interactions with the protease as amide linkages in other peptide analogue inhibitors. The sole substitution of the C-terminal carboxamide of a hydroxyethylene-containing tripeptide analogue with an imidazole group imparts greatly improved pharmacokinetic and oral bioavailability properties on the compound compared to its carboxamide-containing homologue (compound 1). While the oral bioavailability of compound 1 in rats was negligible, compound 2 displayed oral bioavailabilities of 30% and 14%, respectively, in rats and monkeys.

An orally bioavailable HIV-1 protease inhibitor containing an imidazole-derived peptide bond replacement: crystallographic and pharmacokinetic analysis.,Abdel-Meguid SS, Metcalf BW, Carr TJ, Demarsh P, DesJarlais RL, Fisher S, Green DW, Ivanoff L, Lambert DM, Murthy KH, et al. Biochemistry. 1994 Oct 4;33(39):11671-7. PMID:7918383[1]

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

See Also

References

  1. ↑ Abdel-Meguid SS, Metcalf BW, Carr TJ, Demarsh P, DesJarlais RL, Fisher S, Green DW, Ivanoff L, Lambert DM, Murthy KH, et al.. An orally bioavailable HIV-1 protease inhibitor containing an imidazole-derived peptide bond replacement: crystallographic and pharmacokinetic analysis. Biochemistry. 1994 Oct 4;33(39):11671-7. PMID:7918383

1sbg, resolution 2.30Å

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, Eric Martz
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=1sbg&oldid=2060427"