5uoh - Revision history

OCA at 08:51, 9 October 2024

2024-10-09T08:51:29Z

← Older revision		Revision as of 08:51, 9 October 2024
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	<StructureSection load='5uoh' size='340' side='right'caption='[[5uoh]], [[Resolution\|resolution]] 2.61Å' scene=''>		<StructureSection load='5uoh' size='340' side='right'caption='[[5uoh]], [[Resolution\|resolution]] 2.61Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5uoh]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Myctu Myctu~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UOH OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5UOH FirstGlance]. <br>		<table><tr><td colspan='2'>[[5uoh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UOH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UOH FirstGlance]. <br>
	</td></tr><tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~>[[5uno\|5uno]]</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]] 2.609Å</td></tr>
	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Gene~~\|~~Gene:~~]]~~</b></td><td class="sblockDat">caeA, Rv2224c, MTCY427.05c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax~~.~~cgi?mode=Info&srchmode=5~~&~~id=83332 MYCTU])~~</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=5uoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uoh OCA], [https://pdbe.org/5uoh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uoh RCSB], [https://www.ebi.ac.uk/pdbsum/5uoh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uoh 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=5uoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uoh OCA], [~~http~~://pdbe.org/5uoh PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5uoh RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5uoh PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5uoh ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/~~CAEA_MYCTU CAEA_MYCTU~~]~~] Involved~~ in virulence. ~~Catalyzes~~ the ~~cleavage~~ of ~~ester bonds~~. ~~Esterase activity increases with increasing carbon chain length~~ of the ~~substrate~~.<ref>PMID:~~17428787~~</ref>		[https://www.uniprot.org/uniprot/HIP1_MYCTU HIP1_MYCTU] Serine protease that promotes tuberculosis (TB) pathogenesis by promoting the processing and the extracellular release of the M.tuberculosis (Mtb) heat-shock protein GroEL2 (PubMed:18172199, PubMed:24830429, PubMed:28346784). Hip1-dependent cleavage of multimeric GroEL2 results in release of cleaved monomeric GroEL2 into the extracellular milieu. Conversion of multimeric GroEL2 into monomeric GroEL2 is likely to be a mechanism for regulating GroEL2 functions during Mtb pathogenesis (PubMed:24830429). In vitro, exhibits proteolytic activity against synthetic peptides and the general protease substrate azocasein, and exhibits esterase activity against the ester substrate p-nitrophenylbutyrate (PubMed:24830429, PubMed:28346784).<ref>PMID:18172199</ref> <ref>PMID:24830429</ref> <ref>PMID:28346784</ref> Key immunomodulatory virulence factor, which promotes survival in host macrophages and modulates host immune responses (PubMed:18172199, PubMed:21947769, PubMed:24659689). Impacts host innate immune responses by preventing robust macrophage activation (PubMed:18172199, PubMed:21947769). Dampens macrophage pro-inflammatory responses by limiting toll-like receptor 2 (TLR2) activation. It also dampens TLR2-independent activation of the inflammasome and limits secretion of interleukin-18 (IL-18). May act by masking cell surface interactions between TLR2 agonists on Mtb and TLR2 on macrophages (PubMed:21947769). In addition, impacts host adaptive immune responses. It prevents robust maturation of infected dendritic cells (DCs), limits the secretion of key pro-inflammatory cytokines such as IL-12, impairs Ag presentation, and modulates the nature of Ag-specific T-cell responses (PubMed:24659689).<ref>PMID:18172199</ref> <ref>PMID:21947769</ref> <ref>PMID:24659689</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: ~~Myctu~~]]		[[Category: Mycobacterium tuberculosis H37Rv]]
	[[Category: Baikovitz, J]]		[[Category: Baikovitz J]]
	[[Category: Daab, A]]		[[Category: Daab A]]
	[[Category: Dunn~~, B M~~]]		[[Category: Dunn BM]]
	[[Category: Goldfarb, N]]		[[Category: Goldfarb N]]
	[[Category: Liu, D]]		[[Category: Liu D]]
	[[Category: Milne~~, A C~~]]		[[Category: Milne AC]]
	[[Category: Naffin-Olivos~~, J L~~]]		[[Category: Naffin-Olivos JL]]
	[[Category: Petsko~~, G A~~]]		[[Category: Petsko GA]]
	[[Category: Rengarajan, J]]		[[Category: Rengarajan J]]
	[[Category: Ringe, D]]		[[Category: Ringe D]]
	[[Category: White, A]]		[[Category: White A]]
	~~[[Category: Hydrolase]]~~
	~~[[Category: Serine protease~~]]

OCA at 09:31, 4 December 2019

2019-12-04T09:31:21Z

← Older revision		Revision as of 09:31, 4 December 2019
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	==Crystal Structure of Hip1 (Rv2224c) T466A mutant==		==Crystal Structure of Hip1 (Rv2224c) T466A mutant==
	<StructureSection load='5uoh' size='340' side='right' caption='[[5uoh]], [[Resolution\|resolution]] 2.61Å' scene=''>		<StructureSection load='5uoh' size='340' side='right'caption='[[5uoh]], [[Resolution\|resolution]] 2.61Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5uoh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UOH FirstGlance]. <br>		<table><tr><td colspan='2'>[[5uoh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UOH FirstGlance]. <br>
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	</div>		</div>
	<div class="pdbe-citations 5uoh" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5uoh" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Carboxylesterase 3D structures\|Carboxylesterase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Large Structures]]
	[[Category: Myctu]]		[[Category: Myctu]]
	[[Category: Baikovitz, J]]		[[Category: Baikovitz, J]]

OCA at 14:36, 6 November 2017

2017-11-06T14:36:10Z

← Older revision		Revision as of 14:36, 6 November 2017
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	<StructureSection load='5uoh' size='340' side='right' caption='[[5uoh]], [[Resolution\|resolution]] 2.61Å' scene=''>		<StructureSection load='5uoh' size='340' side='right' caption='[[5uoh]], [[Resolution\|resolution]] 2.61Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5uoh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UOH FirstGlance]. <br>		<table><tr><td colspan='2'>[[5uoh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UOH FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5uno\|5uno]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5uno\|5uno]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">caeA, Rv2224c, MTCY427.05c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=5uoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uoh OCA], [http://pdbe.org/5uoh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uoh RCSB], [http://www.ebi.ac.uk/pdbsum/5uoh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uoh 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=5uoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uoh OCA], [http://pdbe.org/5uoh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uoh RCSB], [http://www.ebi.ac.uk/pdbsum/5uoh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uoh ProSAT]</span></td></tr>
	</table>		</table>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Myctu]]
	[[Category: Baikovitz, J]]		[[Category: Baikovitz, J]]
	[[Category: Daab, A]]		[[Category: Daab, A]]

OCA at 11:39, 12 April 2017

2017-04-12T11:39:15Z

← Older revision		Revision as of 11:39, 12 April 2017
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	~~'''Unreleased structure'''~~

	~~The entry~~ 5uoh is ~~ON HOLD~~ ~~until Paper~~ Publication		==Crystal Structure of Hip1 (Rv2224c) T466A mutant==
			<StructureSection load='5uoh' size='340' side='right' caption='[[5uoh]], [[Resolution\|resolution]] 2.61Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[5uoh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UOH FirstGlance]. <br>
			</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5uno\|5uno]]</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=5uoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uoh OCA], [http://pdbe.org/5uoh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uoh RCSB], [http://www.ebi.ac.uk/pdbsum/5uoh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uoh ProSAT]</span></td></tr>
			</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/CAEA_MYCTU CAEA_MYCTU]] Involved in virulence. Catalyzes the cleavage of ester bonds. Esterase activity increases with increasing carbon chain length of the substrate.<ref>PMID:17428787</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The Mycobacterium tuberculosis (Mtb) serine protease Hip1 (hydrolase important for pathogenesis; Rv2224c) promotes tuberculosis (TB) pathogenesis by impairing host immune responses through proteolysis of a protein substrate, Mtb GroEL2. The cell surface localization of Hip1 and its immunomodulatory functions make Hip1 a good drug target for new adjunctive immune therapies for TB. Here, we report the crystal structure of Hip1 to a resolution of 2.6 A and the kinetic studies of the enzyme against model substrates and the protein GroEL2. The structure shows a two-domain protein, one of which contains the catalytic residues that are the signature of a serine protease. Surprisingly, a threonine is located within the active site close enough to hydrogen bond with the catalytic residues Asp463 and His490. Mutation of this residue, Thr466, to alanine established its importance for function. Our studies provide insights into the structure of a member of a novel family of proteases. Knowledge of the Hip1 structure will aid in designing inhibitors that could block Hip1 activity.

	~~Authors:~~ Naffin-Olivos~~, J.L.~~, Daab, A., White, A., Goldfarb~~, N.~~, Milne~~, A.C.~~, Liu, D., Baikovitz, J., Dunn~~, B.M.~~, Rengarajan, J., Petsko, G.A.~~, Ringe, D~~.		Structure Determination of Mycobacterium tuberculosis Serine Protease Hip1 (Rv2224c).,Naffin-Olivos JL, Daab A, White A, Goldfarb NE, Milne AC, Liu D, Baikovitz J, Dunn BM, Rengarajan J, Petsko GA, Ringe D Biochemistry. 2017 Apr 7. doi: 10.1021/acs.biochem.6b01066. PMID:28346784<ref>PMID:28346784</ref>

	~~Description~~: ~~Crystal Structure of Hip1 (Rv2224c) T466A mutant~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	[[Category: ~~Unreleased Structures~~]]		</div>
	[[Category: Dunn, B.M]]		<div class="pdbe-citations 5uoh" style="background-color:#fffaf0;"></div>
	[[Category: ~~Milne~~, ~~A.C~~]]		== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Baikovitz, J]]
			[[Category: Daab, A]]
			[[Category: Dunn, B M]]
			[[Category: Goldfarb, N]]
	[[Category: Liu, D]]		[[Category: Liu, D]]
			[[Category: Milne, A C]]
			[[Category: Naffin-Olivos, J L]]
			[[Category: Petsko, G A]]
	[[Category: Rengarajan, J]]		[[Category: Rengarajan, J]]
	[[Category: Ringe, D]]		[[Category: Ringe, D]]
	[[Category: White, A]]		[[Category: White, A]]
	[[Category: ~~Petsko, G.A~~]]		[[Category: Hydrolase]]
	[[Category: ~~Naffin-Olivos, J.L]]~~		[[Category: Serine protease]]
	~~[[Category: Daab, A]]~~
	~~[[Category: Goldfarb, N]]~~
	~~[[Category: Baikovitz, J~~]]

OCA at 11:14, 5 April 2017

2017-04-05T11:14:50Z

← Older revision		Revision as of 11:14, 5 April 2017
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 5uoh is ON HOLD		The entry 5uoh is ON HOLD until Paper Publication

	Authors: Naffin-Olivos, J.L., Daab, A., White, A., Goldfarb, N., Milne, A.C., Liu, D., Baikovitz, J., Dunn, B.M., Rengarajan, J., Petsko, G.A., Ringe, D.		Authors: Naffin-Olivos, J.L., Daab, A., White, A., Goldfarb, N., Milne, A.C., Liu, D., Baikovitz, J., Dunn, B.M., Rengarajan, J., Petsko, G.A., Ringe, D.

OCA at 19:14, 15 March 2017

2017-03-15T19:14:38Z

← Older revision		Revision as of 19:14, 15 March 2017
Line 7:		Line 7:
	Description: Crystal Structure of Hip1 (Rv2224c) T466A mutant		Description: Crystal Structure of Hip1 (Rv2224c) T466A mutant
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	~~[[Category: White, A]]~~
	~~[[Category: Petsko, G.A]]~~
	~~[[Category: Naffin-Olivos, J.L]]~~
	[[Category: Dunn, B.M]]		[[Category: Dunn, B.M]]
	[[Category: Milne, A.C]]		[[Category: Milne, A.C]]
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	[[Category: Rengarajan, J]]		[[Category: Rengarajan, J]]
	[[Category: Ringe, D]]		[[Category: Ringe, D]]
			[[Category: White, A]]
			[[Category: Petsko, G.A]]
			[[Category: Naffin-Olivos, J.L]]
	[[Category: Daab, A]]		[[Category: Daab, A]]
	[[Category: Goldfarb, N]]		[[Category: Goldfarb, N]]
	[[Category: Baikovitz, J]]		[[Category: Baikovitz, J]]

OCA: Protected "5uoh" [edit=sysop:move=sysop]

2017-03-09T14:43:57Z

Protected "5uoh" [edit=sysop:move=sysop]

← Older revision	Revision as of 14:43, 9 March 2017
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5uoh is ON HOLD Authors: Naffin-Olivos, J.L., Daab, A., White, A., Goldfarb, N., Milne, A.C., Liu, D., Baikovitz, J., Dunn, B.M., Rengarajan, J., Pe...

2017-03-09T14:43:56Z

New page: '''Unreleased structure''' The entry 5uoh is ON HOLD Authors: Naffin-Olivos, J.L., Daab, A., White, A., Goldfarb, N., Milne, A.C., Liu, D., Baikovitz, J., Dunn, B.M., Rengarajan, J., Pe...

New page

'''Unreleased structure'''

The entry 5uoh is ON HOLD

Authors: Naffin-Olivos, J.L., Daab, A., White, A., Goldfarb, N., Milne, A.C., Liu, D., Baikovitz, J., Dunn, B.M., Rengarajan, J., Petsko, G.A., Ringe, D.

Description: Crystal Structure of Hip1 (Rv2224c) T466A mutant
[[Category: Unreleased Structures]]
[[Category: White, A]]
[[Category: Petsko, G.A]]
[[Category: Naffin-Olivos, J.L]]
[[Category: Dunn, B.M]]
[[Category: Milne, A.C]]
[[Category: Liu, D]]
[[Category: Rengarajan, J]]
[[Category: Ringe, D]]
[[Category: Daab, A]]
[[Category: Goldfarb, N]]
[[Category: Baikovitz, J]]