2op0

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2op0.jpg|left|200px]]<br /><applet load="2op0" size="350" color="white" frame="true" align="right" spinBox="true"
+
[[Image:2op0.jpg|left|200px]]
-
caption="2op0, resolution 2.80&Aring;" />
+
 
-
'''Crystal structure of plasmodium falciparum enoyl ACP reductase with triclosan reductase'''<br />
+
{{Structure
 +
|PDB= 2op0 |SIZE=350|CAPTION= <scene name='initialview01'>2op0</scene>, resolution 2.80&Aring;
 +
|SITE=
 +
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene> and <scene name='pdbligand=7PC:2-[4-(AMINOMETHYL)-2-CHLOROPHENOXY]-5-PYRIDIN-2-YLPHENOL'>7PC</scene>
 +
|ACTIVITY= [http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9]
 +
|GENE= FabI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 Plasmodium falciparum])
 +
}}
 +
 
 +
'''Crystal structure of plasmodium falciparum enoyl ACP reductase with triclosan reductase'''
 +
 
==Overview==
==Overview==
Line 7: Line 16:
==About this Structure==
==About this Structure==
-
2OP0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=NAD:'>NAD</scene> and <scene name='pdbligand=7PC:'>7PC</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OP0 OCA].
+
2OP0 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OP0 OCA].
==Reference==
==Reference==
-
X-ray structural analysis of Plasmodium falciparum enoyl acyl carrier protein reductase as a pathway toward the optimization of triclosan antimalarial efficacy., Freundlich JS, Wang F, Tsai HC, Kuo M, Shieh HM, Anderson JW, Nkrumah LJ, Valderramos JC, Yu M, Kumar TR, Valderramos SG, Jacobs WR Jr, Schiehser GA, Jacobus DP, Fidock DA, Sacchettini JC, J Biol Chem. 2007 Aug 31;282(35):25436-44. Epub 2007 Jun 13. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17567585 17567585]
+
X-ray structural analysis of Plasmodium falciparum enoyl acyl carrier protein reductase as a pathway toward the optimization of triclosan antimalarial efficacy., Freundlich JS, Wang F, Tsai HC, Kuo M, Shieh HM, Anderson JW, Nkrumah LJ, Valderramos JC, Yu M, Kumar TR, Valderramos SG, Jacobs WR Jr, Schiehser GA, Jacobus DP, Fidock DA, Sacchettini JC, J Biol Chem. 2007 Aug 31;282(35):25436-44. Epub 2007 Jun 13. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17567585 17567585]
[[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
[[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
[[Category: Plasmodium falciparum]]
[[Category: Plasmodium falciparum]]
Line 22: Line 31:
[[Category: triclosan analog]]
[[Category: triclosan analog]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:21:01 2008''
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:02:35 2008''

Revision as of 16:02, 20 March 2008

Image:2op0.jpg


PDB ID 2op0

Drag the structure with the mouse to rotate
, resolution 2.80Å
Ligands: , and
Gene: FabI (Plasmodium falciparum)
Activity: [acyl-carrier-protein_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number 1.3.1.9
Coordinates: save as pdb, mmCIF, xml



Crystal structure of plasmodium falciparum enoyl ACP reductase with triclosan reductase


Overview

The x-ray crystal structures of five triclosan analogs, in addition to that of the isoniazid-NAD adduct, are described in relation to their integral role in the design of potent inhibitors of the malarial enzyme Plasmodium falciparum enoyl acyl carrier protein reductase (PfENR). Many of the novel 5-substituted analogs exhibit low micromolar potency against in vitro cultures of drug-resistant and drug-sensitive strains of the P. falciparum parasite and inhibit purified PfENR enzyme with IC50 values of <200 nM. This study has significantly expanded the knowledge base with regard to the structure-activity relationship of triclosan while affording gains against cultured parasites and purified PfENR enzyme. In contrast to a recent report in the literature, these results demonstrate the ability to improve the in vitro potency of triclosan significantly by replacing the suboptimal 5-chloro group with larger hydrophobic moieties. The biological and x-ray crystallographic data thus demonstrate the flexibility of the active site and point to future rounds of optimization to improve compound potency against purified enzyme and intracellular Plasmodium parasites.

About this Structure

2OP0 is a Single protein structure of sequence from Plasmodium falciparum. Full crystallographic information is available from OCA.

Reference

X-ray structural analysis of Plasmodium falciparum enoyl acyl carrier protein reductase as a pathway toward the optimization of triclosan antimalarial efficacy., Freundlich JS, Wang F, Tsai HC, Kuo M, Shieh HM, Anderson JW, Nkrumah LJ, Valderramos JC, Yu M, Kumar TR, Valderramos SG, Jacobs WR Jr, Schiehser GA, Jacobus DP, Fidock DA, Sacchettini JC, J Biol Chem. 2007 Aug 31;282(35):25436-44. Epub 2007 Jun 13. PMID:17567585 [[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]

Page seeded by OCA on Thu Mar 20 18:02:35 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2op0"
Personal tools