3fiv
From Proteopedia
(New page: 200px<br /><applet load="3fiv" size="450" color="white" frame="true" align="right" spinBox="true" caption="3fiv, resolution 1.85Å" /> '''CRYSTAL STRUCTURE OF...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:3fiv.gif|left|200px]]<br /><applet load="3fiv" size=" | + | [[Image:3fiv.gif|left|200px]]<br /><applet load="3fiv" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="3fiv, resolution 1.85Å" /> | caption="3fiv, resolution 1.85Å" /> | ||
'''CRYSTAL STRUCTURE OF FELINE IMMUNODEFICIENCY VIRUS PROTEASE COMPLEXED WITH A SUBSTRATE'''<br /> | '''CRYSTAL STRUCTURE OF FELINE IMMUNODEFICIENCY VIRUS PROTEASE COMPLEXED WITH A SUBSTRATE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Crystal structures of complexes of a D30N mutant of feline | + | Crystal structures of complexes of a D30N mutant of feline immunodeficiency virus protease (FIV PR) complexed with a statine-based inhibitor (LP-149), as well as with a substrate based on a modification of this inhibitor (LP-149S), have been solved and refined at resolutions of 2.0 and 1.85 A, respectively. Both the inhibitor and the substrate are bound in the active site of the mutant protease in a similar mode, which also resembles the mode of binding of LP-149 to the native protease. The carbonyl oxygen of the scissile bond in the substrate is not hydrated and is located within the distance of a hydrogen bond to an amido nitrogen atom from one of the two asparagines in the active site of the enzyme. The nitrogen atom of the scissile bond is 3.25 A from the conserved water molecule (Wat301). A model of a tetrahedral intermediate bound to the active site of the native enzyme was built by considering the interactions observed in all three crystal structures of FIV PR. Molecular dynamics simulations of this model bound to native wild-type FIV PR were carried out, to investigate the final stages of the catalytic mechanism of aspartic proteases. |
==About this Structure== | ==About this Structure== | ||
| - | 3FIV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Feline_immunodeficiency_virus Feline immunodeficiency virus] with SO4 and ACE as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 3FIV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Feline_immunodeficiency_virus Feline immunodeficiency virus] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=ACE:'>ACE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FIV OCA]. |
==Reference== | ==Reference== | ||
| Line 25: | Line 25: | ||
[[Category: retroviral protease]] | [[Category: retroviral protease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:09:26 2008'' |
Revision as of 17:09, 21 February 2008
|
CRYSTAL STRUCTURE OF FELINE IMMUNODEFICIENCY VIRUS PROTEASE COMPLEXED WITH A SUBSTRATE
Overview
Crystal structures of complexes of a D30N mutant of feline immunodeficiency virus protease (FIV PR) complexed with a statine-based inhibitor (LP-149), as well as with a substrate based on a modification of this inhibitor (LP-149S), have been solved and refined at resolutions of 2.0 and 1.85 A, respectively. Both the inhibitor and the substrate are bound in the active site of the mutant protease in a similar mode, which also resembles the mode of binding of LP-149 to the native protease. The carbonyl oxygen of the scissile bond in the substrate is not hydrated and is located within the distance of a hydrogen bond to an amido nitrogen atom from one of the two asparagines in the active site of the enzyme. The nitrogen atom of the scissile bond is 3.25 A from the conserved water molecule (Wat301). A model of a tetrahedral intermediate bound to the active site of the native enzyme was built by considering the interactions observed in all three crystal structures of FIV PR. Molecular dynamics simulations of this model bound to native wild-type FIV PR were carried out, to investigate the final stages of the catalytic mechanism of aspartic proteases.
About this Structure
3FIV is a Single protein structure of sequence from Feline immunodeficiency virus with and as ligands. Active as HIV-1 retropepsin, with EC number 3.4.23.16 Full crystallographic information is available from OCA.
Reference
Crystal structures of the inactive D30N mutant of feline immunodeficiency virus protease complexed with a substrate and an inhibitor., Laco GS, Schalk-Hihi C, Lubkowski J, Morris G, Zdanov A, Olson A, Elder JH, Wlodawer A, Gustchina A, Biochemistry. 1997 Sep 2;36(35):10696-708. PMID:9271500
Page seeded by OCA on Thu Feb 21 19:09:26 2008
