6b2p - Revision history

OCA at 14:19, 13 March 2024

OCA — Wed, 13 Mar 2024 14:19:41 GMT

←Older revision		Revision as of 14:19, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='6b2p' size='340' side='right'caption='[[6b2p]], [[Resolution\|resolution]] 3.01Å' scene=''>		<StructureSection load='6b2p' size='340' side='right'caption='[[6b2p]], [[Resolution\|resolution]] 3.01Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6b2p]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B2P OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6B2P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6b2p]] is a 1 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=6B2P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B2P FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=CJJ:5-{5-chloro-4~~-[~~(5-cyclopropyl-1H-pyrazol-~~3~~-yl)amino]pyrimidin-2-yl}thiophene-2-sulfonamide'>CJJ</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]] 3.01Å</td></tr>
-	<tr id='~~activity~~'><td class="sblockLbl"><b>~~Activity~~:</b></td><td class="sblockDat"><~~span class~~='~~plainlinks'>[http~~:~~//en.wikipedia.org/wiki/Non~~-~~specific_serine/threonine_protein_kinase Non~~-~~specific serine/threonine protein kinase], with EC number~~ [~~http://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=~~2~~.7.11.1~~ 2~~.7.11.1]~~ </~~span~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CJJ:5-{5-chloro-4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl}thiophene-2-sulfonamide'>CJJ</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6b2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b2p OCA], [~~http~~://pdbe.org/6b2p PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6b2p RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6b2p PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6b2p ProSAT]</span></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=6b2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b2p OCA], [https://pdbe.org/6b2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b2p RCSB], [https://www.ebi.ac.uk/pdbsum/6b2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b2p ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~PKNB_MYCTO PKNB_MYCTO~~]~~] Protein kinase that regulates many aspects of mycobacterial physiology. Is a key~~ component of a signal transduction pathway that regulates cell growth~~, cell shape~~ and cell division via phosphorylation of target proteins~~.[UniProtKB:P9WI81]~~	+	[https://www.uniprot.org/uniprot/PKNB_MYCTU PKNB_MYCTU] Key component of a signal transduction pathway that regulates cell growth and cell division via phosphorylation of target proteins such as GarA, GlmU, PapA5, PbpA, FhaB (Rv0019c), FhaA (Rv0020c), MviN, PstP, EmbR, Rv1422, Rv1747 and RseA. Shows a strong preference for Thr versus Ser as the phosphoacceptor.<ref>PMID:15985609</ref> <ref>PMID:15978616</ref> <ref>PMID:15987910</ref> <ref>PMID:16817899</ref> <ref>PMID:16980473</ref> <ref>PMID:16436437</ref> <ref>PMID:19826007</ref> <ref>PMID:19121323</ref> <ref>PMID:20025669</ref> <ref>PMID:21423706</ref> <ref>PMID:22275220</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	~~Drug resistant tuberculosis~~ (TB) infections are on the rise and antibiotics that inhibit Mycobacterium tuberculosis through a novel mechanism could be an important component of evolving TB therapy. Protein kinase A (PknA) and protein kinase B (PknB) are both essential serine-threonine kinases in M. tuberculosis. Given the extensive knowledge base in kinase inhibition, these enzymes present an interesting opportunity for antimycobacterial drug discovery. This study focused on targeting both PknA and PknB while improving the selectivity window over related mammalian kinases. Compounds achieved potent inhibition (~~Ki approximately 5 nM~~) of both PknA and PknB. A binding pocket unique to mycobacterial kinases was identified. Substitutions that filled this pocket resulted in a 100-fold differential against a broad selection of mammalian kinases. Reducing lipophilicity improved antimycobacterial activity with the most potent compounds achieving minimum inhibitory concentrations ranging from 3 to 5 muM (1-2 mug/mL) against the H37Ra isolate of M. tuberculosis.	+
-		+
-	~~Mtb PKNA/PKNB Dual Inhibition Provides Selectivity Advantages for Inhibitor Design To Minimize Host Kinase Interactions.,Wang T, Bemis G, Hanzelka B~~, ~~Zuccola H~~, ~~Wynn M~~, ~~Moody CS~~, ~~Green J~~, ~~Locher C, Liu A, Gao H, Xu Y, Wang S, Wang J, Bennani YL, Thomson JA, Muh U ACS Med Chem Lett~~. ~~2017 Nov 28;8(12):1224-1229~~. ~~doi~~:~~, 10.1021~~/~~acsmedchemlett.7b00239. eCollection 2017 Dec 14.~~ PMID:~~29259738~~<ref>PMID:~~29259738~~</ref>	+
-		+
-	~~From MEDLINE®~~/~~PubMed®, a database of the U.S. National Library of Medicine.~~<br>	+
-	</~~div~~>	+
-	<~~div class="pdbe-citations 6b2p" style="background-color~~:~~#fffaf0;"~~></~~div~~>	+

	==See Also==		==See Also==
Line 27:		Line 18:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Non-specific serine/threonine protein kinase~~]]	+	[[Category: Mycobacterium tuberculosis]]
-	[[Category: Zuccola~~, H J]]~~	+	[[Category: Zuccola HJ]]
-	~~[[Category: Drug design]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase-inhibitor complex]]~~	+
-	~~[[Category: Tuberculosis~~]]	+

OCA at 21:35, 28 October 2020

OCA — Wed, 28 Oct 2020 21:35:46 GMT

←Older revision		Revision as of 21:35, 28 October 2020
Line 1:		Line 1:

	==Dual Inhibition of the Essential Protein Kinases A and B in Mycobacterium tuberculosis==		==Dual Inhibition of the Essential Protein Kinases A and B in Mycobacterium tuberculosis==
-	<StructureSection load='6b2p' size='340' side='right' caption='[[6b2p]], [[Resolution\|resolution]] 3.01Å' scene=''>	+	<StructureSection load='6b2p' size='340' side='right'caption='[[6b2p]], [[Resolution\|resolution]] 3.01Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6b2p]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B2P OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6B2P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6b2p]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B2P OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6B2P FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CJJ:5-{5-chloro-4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl}thiophene-2-sulfonamide'>CJJ</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CJJ:5-{5-chloro-4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl}thiophene-2-sulfonamide'>CJJ</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=6b2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b2p OCA], [http://pdbe.org/6b2p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b2p RCSB], [http://www.ebi.ac.uk/pdbsum/6b2p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b2p ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6b2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b2p OCA], [http://pdbe.org/6b2p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b2p RCSB], [http://www.ebi.ac.uk/pdbsum/6b2p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b2p ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6b2p" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6b2p" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Zuccola, H J]]		[[Category: Zuccola, H J]]

OCA at 06:32, 15 February 2018

OCA — Thu, 15 Feb 2018 06:32:32 GMT

←Older revision		Revision as of 06:32, 15 February 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6b2p is ~~ON HOLD~~	+	==Dual Inhibition of the Essential Protein Kinases A and B in Mycobacterium tuberculosis==
		+	<StructureSection load='6b2p' size='340' side='right' caption='[[6b2p]], [[Resolution\|resolution]] 3.01Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6b2p]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B2P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B2P FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CJJ:5-{5-chloro-4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl}thiophene-2-sulfonamide'>CJJ</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=6b2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b2p OCA], [http://pdbe.org/6b2p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b2p RCSB], [http://www.ebi.ac.uk/pdbsum/6b2p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b2p ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PKNB_MYCTO PKNB_MYCTO]] Protein kinase that regulates many aspects of mycobacterial physiology. Is a key component of a signal transduction pathway that regulates cell growth, cell shape and cell division via phosphorylation of target proteins.[UniProtKB:P9WI81]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Drug resistant tuberculosis (TB) infections are on the rise and antibiotics that inhibit Mycobacterium tuberculosis through a novel mechanism could be an important component of evolving TB therapy. Protein kinase A (PknA) and protein kinase B (PknB) are both essential serine-threonine kinases in M. tuberculosis. Given the extensive knowledge base in kinase inhibition, these enzymes present an interesting opportunity for antimycobacterial drug discovery. This study focused on targeting both PknA and PknB while improving the selectivity window over related mammalian kinases. Compounds achieved potent inhibition (Ki approximately 5 nM) of both PknA and PknB. A binding pocket unique to mycobacterial kinases was identified. Substitutions that filled this pocket resulted in a 100-fold differential against a broad selection of mammalian kinases. Reducing lipophilicity improved antimycobacterial activity with the most potent compounds achieving minimum inhibitory concentrations ranging from 3 to 5 muM (1-2 mug/mL) against the H37Ra isolate of M. tuberculosis.

-	~~Authors:~~ Zuccola, H.J.	+	Mtb PKNA/PKNB Dual Inhibition Provides Selectivity Advantages for Inhibitor Design To Minimize Host Kinase Interactions.,Wang T, Bemis G, Hanzelka B, Zuccola H, Wynn M, Moody CS, Green J, Locher C, Liu A, Gao H, Xu Y, Wang S, Wang J, Bennani YL, Thomson JA, Muh U ACS Med Chem Lett. 2017 Nov 28;8(12):1224-1229. doi:, 10.1021/acsmedchemlett.7b00239. eCollection 2017 Dec 14. PMID:29259738<ref>PMID:29259738</ref>

-	~~Description: Dual Inhibition~~ of the ~~Essential Protein Kinases A and B in Mycobacterium tuberculosis~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Zuccola, H.J]]	+	<div class="pdbe-citations 6b2p" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Zuccola, H J]]
		+	[[Category: Drug design]]
		+	[[Category: Kinase]]
		+	[[Category: Transferase-inhibitor complex]]
		+	[[Category: Tuberculosis]]

OCA at 08:11, 4 October 2017

OCA — Wed, 04 Oct 2017 08:11:00 GMT

←Older revision		Revision as of 08:11, 4 October 2017
Line 3:		Line 3:
	The entry 6b2p is ON HOLD		The entry 6b2p is ON HOLD

-	Authors: ~~Zuccola, H.J.,~~ Zuccola, H.J.	+	Authors: Zuccola, H.J.

	Description: Dual Inhibition of the Essential Protein Kinases A and B in Mycobacterium tuberculosis		Description: Dual Inhibition of the Essential Protein Kinases A and B in Mycobacterium tuberculosis
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Zuccola, H.J]]		[[Category: Zuccola, H.J]]

OCA: Protected "6b2p" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 17:06:44 GMT

Protected "6b2p" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:06, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 6b2p is ON HOLD Authors: Zuccola, H.J., Zuccola, H.J. Description: Dual Inhibition of the Essential Protein Kinases A and B in Mycobacterium tuberc...

OCA — Wed, 27 Sep 2017 17:06:43 GMT

New page: '''Unreleased structure''' The entry 6b2p is ON HOLD Authors: Zuccola, H.J., Zuccola, H.J. Description: Dual Inhibition of the Essential Protein Kinases A and B in Mycobacterium tuberc...

New page

'''Unreleased structure'''

The entry 6b2p is ON HOLD

Authors: Zuccola, H.J., Zuccola, H.J.

Description: Dual Inhibition of the Essential Protein Kinases A and B in Mycobacterium tuberculosis
[[Category: Unreleased Structures]]
[[Category: Zuccola, H.J]]