1pwp

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (09:49, 16 August 2023) (edit) (undo)
 
(9 intermediate revisions not shown.)
Line 1: Line 1:
-
{{Seed}}
 
-
[[Image:1pwp.png|left|200px]]
 
-
<!--
+
==Crystal Structure of the Anthrax Lethal Factor complexed with Small Molecule Inhibitor NSC 12155==
-
The line below this paragraph, containing "STRUCTURE_1pwp", creates the "Structure Box" on the page.
+
<StructureSection load='1pwp' size='340' side='right'caption='[[1pwp]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
-
You may change the PDB parameter (which sets the PDB file loaded into the applet)
+
== Structural highlights ==
-
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+
<table><tr><td colspan='2'>[[1pwp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PWP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PWP FirstGlance]. <br>
-
or leave the SCENE parameter empty for the default display.
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
-
-->
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NSC:N,N-BIS(4-AMINO-2-METHYLQUINOLIN-6-YL)UREA'>NSC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-
{{STRUCTURE_1pwp| PDB=1pwp | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1pwp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pwp OCA], [https://pdbe.org/1pwp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pwp RCSB], [https://www.ebi.ac.uk/pdbsum/1pwp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pwp ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/LEF_BACAN LEF_BACAN] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. LF is the lethal factor that, when associated with PA, causes death. LF is not toxic by itself. It is a protease that cleaves the N-terminal of most dual specificity mitogen-activated protein kinase kinases (MAPKKs or MAP2Ks) (except for MAP2K5). Cleavage invariably occurs within the N-terminal proline-rich region preceding the kinase domain, thus disrupting a sequence involved in directing specific protein-protein interactions necessary for the assembly of signaling complexes. There may be other cytosolic targets of LF involved in cytotoxicity. The proteasome may mediate a toxic process initiated by LF in the cell cytosol involving degradation of unidentified molecules that are essential for macrophage homeostasis. This is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates.<ref>PMID:9563949</ref> <ref>PMID:9703991</ref> <ref>PMID:10475971</ref> <ref>PMID:11104681</ref> <ref>PMID:10338520</ref>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
The virulent spore-forming bacterium Bacillus anthracis secretes anthrax toxin composed of protective antigen (PA), lethal factor (LF) and edema factor (EF). LF is a Zn-dependent metalloprotease that inactivates key signaling molecules, such as mitogen-activated protein kinase kinases (MAPKK), to ultimately cause cell death. We report here the identification of small molecule (nonpeptidic) inhibitors of LF. Using a two-stage screening assay, we determined the LF inhibitory properties of 19 compounds. Here, we describe six inhibitors on the basis of a pharmacophoric relationship determined using X-ray crystallographic data, molecular docking studies and three-dimensional (3D) database mining from the US National Cancer Institute (NCI) chemical repository. Three of these compounds have K(i) values in the 0.5-5 microM range and show competitive inhibition. These molecular scaffolds may be used to develop therapeutically viable inhibitors of LF.
-
===Crystal Structure of the Anthrax Lethal Factor complexed with Small Molecule Inhibitor NSC 12155===
+
Identification of small molecule inhibitors of anthrax lethal factor.,Panchal RG, Hermone AR, Nguyen TL, Wong TY, Schwarzenbacher R, Schmidt J, Lane D, McGrath C, Turk BE, Burnett J, Aman MJ, Little S, Sausville EA, Zaharevitz DW, Cantley LC, Liddington RC, Gussio R, Bavari S Nat Struct Mol Biol. 2004 Jan;11(1):67-72. Epub 2003 Dec 29. PMID:14718925<ref>PMID:14718925</ref>
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 1pwp" style="background-color:#fffaf0;"></div>
-
<!--
+
==See Also==
-
The line below this paragraph, {{ABSTRACT_PUBMED_14718925}}, adds the Publication Abstract to the page
+
*[[Anthrax lethal factor 3D structures|Anthrax lethal factor 3D structures]]
-
(as it appears on PubMed at http://www.pubmed.gov), where 14718925 is the PubMed ID number.
+
== References ==
-
-->
+
<references/>
-
{{ABSTRACT_PUBMED_14718925}}
+
__TOC__
-
 
+
</StructureSection>
-
==About this Structure==
+
-
1PWP is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PWP OCA].
+
-
 
+
-
==Reference==
+
-
Identification of small molecule inhibitors of anthrax lethal factor., Panchal RG, Hermone AR, Nguyen TL, Wong TY, Schwarzenbacher R, Schmidt J, Lane D, McGrath C, Turk BE, Burnett J, Aman MJ, Little S, Sausville EA, Zaharevitz DW, Cantley LC, Liddington RC, Gussio R, Bavari S, Nat Struct Mol Biol. 2004 Jan;11(1):67-72. Epub 2003 Dec 29. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14718925 14718925]
+
-
[[Category: Anthrax lethal factor endopeptidase]]
+
[[Category: Bacillus anthracis]]
[[Category: Bacillus anthracis]]
-
[[Category: Single protein]]
+
[[Category: Large Structures]]
-
[[Category: Liddington, R C.]]
+
[[Category: Liddington RC]]
-
[[Category: Schwarzenbacher, R.]]
+
[[Category: Schwarzenbacher R]]
-
[[Category: Wong, T Y.]]
+
[[Category: Wong TY]]
-
[[Category: Anthrax toxin]]
+
-
[[Category: Lethal factor]]
+
-
[[Category: Small molecule inhibitor]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 11:06:19 2008''
+

Current revision

Crystal Structure of the Anthrax Lethal Factor complexed with Small Molecule Inhibitor NSC 12155

PDB ID 1pwp

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1pwp"
Personal tools