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| - | [[Image:2z9i.jpg|left|200px]] | |
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| - | <!--
| + | ==Crystal structure of RV0983 from Mycobacterium tuberculosis- Proteolytically active form== |
| - | The line below this paragraph, containing "STRUCTURE_2z9i", creates the "Structure Box" on the page.
| + | <StructureSection load='2z9i' size='340' side='right'caption='[[2z9i]], [[Resolution|resolution]] 2.00Å' 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'>[[2z9i]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z9I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Z9I 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]] 2Å</td></tr> |
| - | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | {{STRUCTURE_2z9i| PDB=2z9i | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2z9i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z9i OCA], [https://pdbe.org/2z9i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2z9i RCSB], [https://www.ebi.ac.uk/pdbsum/2z9i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2z9i ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PEPD_MYCTU PEPD_MYCTU] Required for virulence (PubMed:18479146). Acts both as a protease, which degrades and/or refolds damaged substrate targets, and as a chaperone (PubMed:18479146, PubMed:20061478). Plays an important role in the stress response network mediated through the two-component regulatory system MprAB and SigE signaling networks (PubMed:20061478). May utilize its PDZ domain to recognize and process misfolded proteins at the cell membrane, leading to activation of the MprAB and SigE signaling pathways and subsequent establishment of a positive feedback loop that facilitates bacterial adaptation (PubMed:20061478). Interacts with and potentially cleaves several proteins, including the 35 kDa antigen PspA (PubMed:21445360). Proteolytic cleavage of PspA may help to maintain cell envelope homeostasis in Mycobacterium and regulate specific stress response pathways during periods of extracytoplasmic stress (PubMed:21445360). In vitro, exhibits proteolytic activity against the artificial substrate beta-casein (PubMed:18479146, PubMed:20061478).<ref>PMID:18479146</ref> <ref>PMID:20061478</ref> <ref>PMID:21445360</ref> |
| | + | == 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/z9/2z9i_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=2z9i ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The high-temperature requirement A (HtrA) family of serine proteases has been shown to play an important role in the environmental and cellular stress damage control system in Escherichia coli. Mycobacterium tuberculosis ( Mtb) has three putative HtrA-like proteases, HtrA1, HtrA2, and HtrA3. The deletion of htrA2 gives attenuated virulence in a mouse model of TB. Biochemical analysis reveals that HtrA2 can function both as a protease and as a chaperone. The three-dimensional structure of HtrA2 determined at 2.0 A resolution shows that the protease domains form the central core of the trimer and the PDZ domains extend to the periphery. Unlike E. coli DegS and DegP, the protease is naturally active due to the formation of the serine protease-like catalytic triad and its uniquely designed oxyanion hole. Both protease and PDZ binding pockets of each HtrA2 molecule are occupied by autoproteolytic peptide products and reveal clues for a novel autoregulatory mechanism that might have significant importance in HtrA-associated virulence of Mtb. |
| | | | |
| - | '''Crystal structure of RV0983 from Mycobacterium tuberculosis- Proteolytically active form'''
| + | Structure and function of the virulence-associated high-temperature requirement A of Mycobacterium tuberculosis.,Mohamedmohaideen NN, Palaninathan SK, Morin PM, Williams BJ, Braunstein M, Tichy SE, Locker J, Russell DH, Jacobs WR Jr, Sacchettini JC Biochemistry. 2008 Jun 10;47(23):6092-102. Epub 2008 May 15. PMID:18479146<ref>PMID:18479146</ref> |
| - | | + | |
| - | | + | |
| - | ==Overview==
| + | |
| - | The high-temperature requirement A (HtrA) family of serine proteases has been shown to play an important role in the environmental and cellular stress damage control system in Escherichia coli. Mycobacterium tuberculosis ( Mtb) has three putative HtrA-like proteases, HtrA1, HtrA2, and HtrA3. The deletion of htrA2 gives attenuated virulence in a mouse model of TB. Biochemical analysis reveals that HtrA2 can function both as a protease and as a chaperone. The three-dimensional structure of HtrA2 determined at 2.0 A resolution shows that the protease domains form the central core of the trimer and the PDZ domains extend to the periphery. Unlike E. coli DegS and DegP, the protease is naturally active due to the formation of the serine protease-like catalytic triad and its uniquely designed oxyanion hole. Both protease and PDZ binding pockets of each HtrA2 molecule are occupied by autoproteolytic peptide products and reveal clues for a novel autoregulatory mechanism that might have significant importance in HtrA-associated virulence of Mtb.
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 2Z9I is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z9I OCA].
| + | </div> |
| | + | <div class="pdbe-citations 2z9i" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | Structure and function of the virulence-associated high-temperature requirement A of Mycobacterium tuberculosis., Mohamedmohaideen NN, Palaninathan SK, Morin PM, Williams BJ, Braunstein M, Tichy SE, Locker J, Russell DH, Jacobs WR Jr, Sacchettini JC, Biochemistry. 2008 Jun 10;47(23):6092-102. Epub 2008 May 15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18479146 18479146]
| + | *[[Proteins from Mycobacterium tuberculosis|Proteins from Mycobacterium tuberculosis]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mycobacterium tuberculosis]] | | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Protein complex]]
| + | [[Category: Mohamedmohaideen NN]] |
| - | [[Category: Mohamedmohaideen, N N.]] | + | [[Category: Palaninathan SK]] |
| - | [[Category: Palaninathan, S K.]] | + | [[Category: Sacchettini JC]] |
| - | [[Category: Sacchettini, J C.]] | + | |
| - | [[Category: Htra]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 11 10:46:02 2008''
| + | |
| Structural highlights
Function
PEPD_MYCTU Required for virulence (PubMed:18479146). Acts both as a protease, which degrades and/or refolds damaged substrate targets, and as a chaperone (PubMed:18479146, PubMed:20061478). Plays an important role in the stress response network mediated through the two-component regulatory system MprAB and SigE signaling networks (PubMed:20061478). May utilize its PDZ domain to recognize and process misfolded proteins at the cell membrane, leading to activation of the MprAB and SigE signaling pathways and subsequent establishment of a positive feedback loop that facilitates bacterial adaptation (PubMed:20061478). Interacts with and potentially cleaves several proteins, including the 35 kDa antigen PspA (PubMed:21445360). Proteolytic cleavage of PspA may help to maintain cell envelope homeostasis in Mycobacterium and regulate specific stress response pathways during periods of extracytoplasmic stress (PubMed:21445360). In vitro, exhibits proteolytic activity against the artificial substrate beta-casein (PubMed:18479146, PubMed:20061478).[1] [2] [3]
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 high-temperature requirement A (HtrA) family of serine proteases has been shown to play an important role in the environmental and cellular stress damage control system in Escherichia coli. Mycobacterium tuberculosis ( Mtb) has three putative HtrA-like proteases, HtrA1, HtrA2, and HtrA3. The deletion of htrA2 gives attenuated virulence in a mouse model of TB. Biochemical analysis reveals that HtrA2 can function both as a protease and as a chaperone. The three-dimensional structure of HtrA2 determined at 2.0 A resolution shows that the protease domains form the central core of the trimer and the PDZ domains extend to the periphery. Unlike E. coli DegS and DegP, the protease is naturally active due to the formation of the serine protease-like catalytic triad and its uniquely designed oxyanion hole. Both protease and PDZ binding pockets of each HtrA2 molecule are occupied by autoproteolytic peptide products and reveal clues for a novel autoregulatory mechanism that might have significant importance in HtrA-associated virulence of Mtb.
Structure and function of the virulence-associated high-temperature requirement A of Mycobacterium tuberculosis.,Mohamedmohaideen NN, Palaninathan SK, Morin PM, Williams BJ, Braunstein M, Tichy SE, Locker J, Russell DH, Jacobs WR Jr, Sacchettini JC Biochemistry. 2008 Jun 10;47(23):6092-102. Epub 2008 May 15. PMID:18479146[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mohamedmohaideen NN, Palaninathan SK, Morin PM, Williams BJ, Braunstein M, Tichy SE, Locker J, Russell DH, Jacobs WR Jr, Sacchettini JC. Structure and function of the virulence-associated high-temperature requirement A of Mycobacterium tuberculosis. Biochemistry. 2008 Jun 10;47(23):6092-102. Epub 2008 May 15. PMID:18479146 doi:10.1021/bi701929m
- ↑ White MJ, He H, Penoske RM, Twining SS, Zahrt TC. PepD participates in the mycobacterial stress response mediated through MprAB and SigE. J Bacteriol. 2010 Mar;192(6):1498-510. PMID:20061478 doi:10.1128/JB.01167-09
- ↑ White MJ, Savaryn JP, Bretl DJ, He H, Penoske RM, Terhune SS, Zahrt TC. The HtrA-like serine protease PepD interacts with and modulates the Mycobacterium tuberculosis 35-kDa antigen outer envelope protein. PLoS One. 2011 Mar 22;6(3):e18175. PMID:21445360 doi:10.1371/journal.pone.0018175
- ↑ Mohamedmohaideen NN, Palaninathan SK, Morin PM, Williams BJ, Braunstein M, Tichy SE, Locker J, Russell DH, Jacobs WR Jr, Sacchettini JC. Structure and function of the virulence-associated high-temperature requirement A of Mycobacterium tuberculosis. Biochemistry. 2008 Jun 10;47(23):6092-102. Epub 2008 May 15. PMID:18479146 doi:10.1021/bi701929m
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