3mhz

From Proteopedia

(Difference between revisions)

Revision as of 08:53, 6 September 2023

1.7A structure of 2-fluorohistidine labeled Protective Antigen

Structural highlights

3mhz is a 1 chain structure with sequence from Bacillus anthracis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.7Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PAG_BACAN One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. PA binds to a receptor (ATR) in sensitive eukaryotic cells, thereby facilitating the translocation of the enzymatic toxin components, edema factor and lethal factor, across the target cell membrane. PA associated with LF causes death when injected, PA associated with EF produces edema. PA induces immunity to infection with anthrax.

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

The protective antigen (PA) component of the anthrax toxin forms pores within the low pH environment of host endosomes through mechanisms that are poorly understood. It has been proposed that pore formation is dependent on histidine protonation. In previous work, we biosynthetically incorporated 2-fluorohistidine (2-FHis), an isosteric analogue of histidine with a significantly reduced pK(a) ( approximately 1), into PA and showed that the pH-dependent conversion from the soluble prepore to a pore was unchanged. However, we also observed that 2-FHisPA was nonfunctional in the ability to mediate cytotoxicity of CHO-K1 cells by LF(N)-DTA and was defective in translocation through planar lipid bilayers. Here, we show that the defect in cytotoxicity is due to both a defect in translocation and, when bound to the host cellular receptor, an inability to undergo low pH-induced pore formation. Combining X-ray crystallography with hydrogen-deuterium (H-D) exchange mass spectrometry, our studies lead to a model in which hydrogen bonds to the histidine ring are strengthened by receptor binding. The combination of both fluorination and receptor binding is sufficient to block low pH-induced pore formation.

Evidence that histidine protonation of receptor-bound anthrax protective antigen is a trigger for pore formation.,Wimalasena DS, Janowiak BE, Lovell S, Miyagi M, Sun J, Zhou H, Hajduch J, Pooput C, Kirk KL, Battaile KP, Bann JG Biochemistry. 2010 Aug 24;49(33):6973-83. PMID:20672855^[1]

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

References

↑ Wimalasena DS, Janowiak BE, Lovell S, Miyagi M, Sun J, Zhou H, Hajduch J, Pooput C, Kirk KL, Battaile KP, Bann JG. Evidence that histidine protonation of receptor-bound anthrax protective antigen is a trigger for pore formation. Biochemistry. 2010 Aug 24;49(33):6973-83. PMID:20672855 doi:10.1021/bi100647z

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3mhz"

@@ Line 1: / Line 1: @@
 ==1.7A structure of 2-fluorohistidine labeled Protective Antigen==
-<StructureSection load='3mhz' size='340' side='right' caption='[[3mhz]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+<StructureSection load='3mhz' size='340' side='right'caption='[[3mhz]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3mhz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_cereus_var._anthracis"_(cohn_1872)_smith_et_al._1946 "bacillus cereus var. anthracis" (cohn 1872) smith et al. 1946]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MHZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MHZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3mhz]] is a 1 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=3MHZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MHZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=2HF:2-FLUORO-L-HISTIDINE'>2HF</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2HF:2-FLUORO-L-HISTIDINE'>2HF</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pagA, pag, pXO1-110, BXA0164, GBAA_pXO1_0164 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 "Bacillus cereus var. anthracis" (Cohn 1872) Smith et al. 1946])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3mhz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mhz OCA], [https://pdbe.org/3mhz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mhz RCSB], [https://www.ebi.ac.uk/pdbsum/3mhz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mhz ProSAT]</span></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=3mhz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mhz OCA], [http://pdbe.org/3mhz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3mhz RCSB], [http://www.ebi.ac.uk/pdbsum/3mhz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3mhz ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PAG_BACAN PAG_BACAN]] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. PA binds to a receptor (ATR) in sensitive eukaryotic cells, thereby facilitating the translocation of the enzymatic toxin components, edema factor and lethal factor, across the target cell membrane. PA associated with LF causes death when injected, PA associated with EF produces edema. PA induces immunity to infection with anthrax.
+[https://www.uniprot.org/uniprot/PAG_BACAN PAG_BACAN] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. PA binds to a receptor (ATR) in sensitive eukaryotic cells, thereby facilitating the translocation of the enzymatic toxin components, edema factor and lethal factor, across the target cell membrane. PA associated with LF causes death when injected, PA associated with EF produces edema. PA induces immunity to infection with anthrax.
 == 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/mh/3mhz_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mh/3mhz_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 34: / Line 33: @@
 __TOC__
 </StructureSection>
-[[Category: Bann, J G]]
+[[Category: Bacillus anthracis]]
-[[Category: Battaile, K P]]
+[[Category: Large Structures]]
-[[Category: Hajduch, J]]
+[[Category: Bann JG]]
-[[Category: Janowiak, B E]]
+[[Category: Battaile KP]]
-[[Category: Kirk, K L]]
+[[Category: Hajduch J]]
-[[Category: Lovell, S]]
+[[Category: Janowiak BE]]
-[[Category: Miyagi, M]]
+[[Category: Kirk KL]]
-[[Category: Pooput, C]]
+[[Category: Lovell S]]
-[[Category: Sun, J]]
+[[Category: Miyagi M]]
-[[Category: Wimalasena, D S]]
+[[Category: Pooput C]]
-[[Category: 2-fluorohistidine]]
+[[Category: Sun J]]
-[[Category: Anthrax]]
+[[Category: Wimalasena DS]]
-[[Category: Histidine]]
-[[Category: Hydrogen bonding]]
-[[Category: Pore]]
-[[Category: Receptor]]
-[[Category: Toxin]]

3mhz

From Proteopedia

Revision as of 08:53, 6 September 2023

1.7A structure of 2-fluorohistidine labeled Protective Antigen

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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