5cpf - Revision history

OCA at 08:39, 27 September 2023

2023-09-27T08:39:46Z

←Older revision		Revision as of 08:39, 27 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5cpf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CPF FirstGlance]. <br>		<table><tr><td colspan='2'>[[5cpf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CPF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=53K:2-(2-METHYLPHENOXY)-5-[(4-PHENYL-1H-1,2,3-TRIAZOL-1-YL)METHYL]PHENOL'>53K</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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]] 3.409Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=53K:2-(2-METHYLPHENOXY)-5-[(4-PHENYL-1H-1,2,3-TRIAZOL-1-YL)METHYL]PHENOL'>53K</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></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=5cpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cpf OCA], [https://pdbe.org/5cpf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cpf RCSB], [https://www.ebi.ac.uk/pdbsum/5cpf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cpf 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=5cpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cpf OCA], [https://pdbe.org/5cpf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cpf RCSB], [https://www.ebi.ac.uk/pdbsum/5cpf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cpf ProSAT]</span></td></tr>
	</table>		</table>

OCA at 12:22, 14 June 2023

2023-06-14T12:22:07Z

←Older revision		Revision as of 12:22, 14 June 2023
Line 3:		Line 3:
	<StructureSection load='5cpf' size='340' side='right'caption='[[5cpf]], [[Resolution\|resolution]] 3.41Å' scene=''>		<StructureSection load='5cpf' size='340' side='right'caption='[[5cpf]], [[Resolution\|resolution]] 3.41Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5cpf]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Mycto Mycto~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CPF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5CPF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5cpf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CPF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=53K:2-(2-METHYLPHENOXY)-5-[(4-PHENYL-1H-1,2,3-TRIAZOL-1-YL)METHYL]PHENOL'>53K</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=53K:2-(2-METHYLPHENOXY)-5-[(4-PHENYL-1H-1,2,3-TRIAZOL-1-YL)METHYL]PHENOL'>53K</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5coq\|5coq]], [[5cp8\|5cp8]]</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=5cpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cpf OCA], [https://pdbe.org/5cpf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cpf RCSB], [https://www.ebi.ac.uk/pdbsum/5cpf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cpf ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">inhA, MT1531 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83331 MYCTO])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </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=5cpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cpf OCA], [~~http~~://pdbe.org/5cpf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5cpf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5cpf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5cpf ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/INHA_MYCTO INHA_MYCTO]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Mycto~~]]	+	[[Category: Mycobacterium tuberculosis CDC1551]]
-	[[Category: Bommineni~~, G R~~]]	+	[[Category: Bommineni GR]]
-	[[Category: Garcia-Diaz, M]]	+	[[Category: Garcia-Diaz M]]
-	[[Category: Lai, C T]]	+	[[Category: Lai C-T]]
-	[[Category: Li, H J]]	+	[[Category: Li H-J]]
-	[[Category: Pan, P]]	+	[[Category: Pan P]]
-	[[Category: Perrone, V]]	+	[[Category: Perrone V]]
-	[[Category: Shah, S]]	+	[[Category: Shah S]]
-	[[Category: Simmerling, C]]	+	[[Category: Simmerling C]]
-	[[Category: Tonge~~, P J~~]]	+	[[Category: Tonge PJ]]
-	[[Category: Yu, W]]	+	[[Category: Yu W]]
-	~~[[Category: Fatty acid biosynthesis inhibition substrate binding loop conformation free energy calculation]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 08:55, 4 December 2019

2019-12-04T08:55:16Z

←Older revision		Revision as of 08:55, 4 December 2019
Line 1:		Line 1:

	==Compensation of the effect of isoleucine to alanine mutation by designed inhibition in the InhA enzyme==		==Compensation of the effect of isoleucine to alanine mutation by designed inhibition in the InhA enzyme==
-	<StructureSection load='5cpf' size='340' side='right' caption='[[5cpf]], [[Resolution\|resolution]] 3.41Å' scene=''>	+	<StructureSection load='5cpf' size='340' side='right'caption='[[5cpf]], [[Resolution\|resolution]] 3.41Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5cpf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycto Mycto]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CPF FirstGlance]. <br>		<table><tr><td colspan='2'>[[5cpf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycto Mycto]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CPF FirstGlance]. <br>
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5cpf" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5cpf" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Enoyl-Acyl-Carrier Protein Reductase 3D structures\|Enoyl-Acyl-Carrier Protein Reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Mycto]]		[[Category: Mycto]]
	[[Category: Bommineni, G R]]		[[Category: Bommineni, G R]]

OCA at 12:28, 6 November 2017

2017-11-06T12:28:57Z

←Older revision		Revision as of 12:28, 6 November 2017
Line 3:		Line 3:
	<StructureSection load='5cpf' size='340' side='right' caption='[[5cpf]], [[Resolution\|resolution]] 3.41Å' scene=''>		<StructureSection load='5cpf' size='340' side='right' caption='[[5cpf]], [[Resolution\|resolution]] 3.41Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5cpf]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CPF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5cpf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycto Mycto]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CPF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=53K:2-(2-METHYLPHENOXY)-5-[(4-PHENYL-1H-1,2,3-TRIAZOL-1-YL)METHYL]PHENOL'>53K</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=53K:2-(2-METHYLPHENOXY)-5-[(4-PHENYL-1H-1,2,3-TRIAZOL-1-YL)METHYL]PHENOL'>53K</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5coq\|5coq]], [[5cp8\|5cp8]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5coq\|5coq]], [[5cp8\|5cp8]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">inhA, MT1531 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83331 MYCTO])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </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=5cpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cpf OCA], [http://pdbe.org/5cpf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cpf RCSB], [http://www.ebi.ac.uk/pdbsum/5cpf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cpf 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=5cpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cpf OCA], [http://pdbe.org/5cpf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cpf RCSB], [http://www.ebi.ac.uk/pdbsum/5cpf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cpf ProSAT]</span></td></tr>
Line 18:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5cpf" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5cpf" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Enoyl-Acyl-Carrier Protein Reductase\|Enoyl-Acyl-Carrier Protein Reductase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Mycto]]
	[[Category: Bommineni, G R]]		[[Category: Bommineni, G R]]
	[[Category: Garcia-Diaz, M]]		[[Category: Garcia-Diaz, M]]

OCA at 14:16, 24 May 2017

2017-05-24T14:16:44Z

←Older revision		Revision as of 14:16, 24 May 2017
Line 1:		Line 1:
		+
	==Compensation of the effect of isoleucine to alanine mutation by designed inhibition in the InhA enzyme==		==Compensation of the effect of isoleucine to alanine mutation by designed inhibition in the InhA enzyme==
	<StructureSection load='5cpf' size='340' side='right' caption='[[5cpf]], [[Resolution\|resolution]] 3.41Å' scene=''>		<StructureSection load='5cpf' size='340' side='right' caption='[[5cpf]], [[Resolution\|resolution]] 3.41Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5coq\|5coq]], [[5cp8\|5cp8]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5coq\|5coq]], [[5cp8\|5cp8]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </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=5cpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cpf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5cpf RCSB], [http://www.ebi.ac.uk/pdbsum/5cpf PDBsum]</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=5cpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cpf OCA], [http://pdbe.org/5cpf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cpf RCSB], [http://www.ebi.ac.uk/pdbsum/5cpf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cpf ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 16:		Line 17:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 5cpf" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Enoyl-Acyl-Carrier Protein Reductase\|Enoyl-Acyl-Carrier Protein Reductase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 14:42, 12 August 2015

2015-08-12T14:42:02Z

←Older revision		Revision as of 14:42, 12 August 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Compensation of the effect of isoleucine to alanine mutation by designed inhibition in the InhA enzyme==
		+	<StructureSection load='5cpf' size='340' side='right' caption='[[5cpf]], [[Resolution\|resolution]] 3.41Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5cpf]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CPF FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=53K:2-(2-METHYLPHENOXY)-5-[(4-PHENYL-1H-1,2,3-TRIAZOL-1-YL)METHYL]PHENOL'>53K</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5coq\|5coq]], [[5cp8\|5cp8]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </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=5cpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cpf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5cpf RCSB], [http://www.ebi.ac.uk/pdbsum/5cpf PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Slow-onset enzyme inhibitors are the subject of considerable interest as an approach to increasing the potency of pharmaceutical compounds by extending the residence time of the inhibitor on the target (the lifetime of the drug-receptor complex). However, rational modulation of residence time presents significant challenges because it requires additional mechanistic insight, such as the nature of the transition state for postbinding isomerization. Our previous work, based on X-ray crystallography, enzyme kinetics, and molecular dynamics simulation, suggested that the slow step in inhibition of the Mycobacterium tuberculosis enoyl-ACP reductase InhA involves a change in the conformation of the substrate binding loop from an open state in the initial enzyme-inhibitor complex to a closed state in the final enzyme-inhibitor complex. Here, we use multidimensional free energy landscapes for loop isomerization to obtain a computational model for the transition state. The results suggest that slow-onset inhibitors crowd key side chains on helices that slide past each other during isomerization, resulting in a steric clash. The landscapes become significantly flatter when residues involved in the steric clash are replaced with alanine. Importantly, this lower barrier can be increased by rational inhibitor redesign to restore the steric clash. Crystallographic studies and enzyme kinetics confirm the predicted effects on loop structure and flexibility, as well as inhibitor residence time. These loss and regain of function studies validate our mechanistic hypothesis for interactions controlling substrate binding loop isomerization, providing a platform for the future design of inhibitors with longer residence times and better in vivo potency. Similar opportunities for slow-onset inhibition via the same mechanism are identified in other pathogens.

-	~~The entry 5cpf is ON HOLD~~	+	Rational Modulation of the Induced-Fit Conformational Change for Slow-Onset Inhibition in Mycobacterium tuberculosis InhA.,Lai CT, Li HJ, Yu W, Shah S, Bommineni GR, Perrone V, Garcia-Diaz M, Tonge PJ, Simmerling C Biochemistry. 2015 Aug 4;54(30):4683-91. doi: 10.1021/acs.biochem.5b00284. Epub, 2015 Jul 24. PMID:26147157<ref>PMID:26147157</ref>

-	~~Authors: Li~~, H.-J.~~, Pan, P~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Compensation of the effect of isoleucine to alanine mutation by designed inhibition in the InhA enzyme~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
-	[[Category: Li, H.-J]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Bommineni, G R]]
		+	[[Category: Garcia-Diaz, M]]
		+	[[Category: Lai, C T]]
		+	[[Category: Li, H J]]
	[[Category: Pan, P]]		[[Category: Pan, P]]
		+	[[Category: Perrone, V]]
		+	[[Category: Shah, S]]
		+	[[Category: Simmerling, C]]
		+	[[Category: Tonge, P J]]
		+	[[Category: Yu, W]]
		+	[[Category: Fatty acid biosynthesis inhibition substrate binding loop conformation free energy calculation]]
		+	[[Category: Oxidoreductase]]

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

2015-07-29T13:41:03Z

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

←Older revision

Revision as of 13:41, 29 July 2015

OCA: New page: '''Unreleased structure''' The entry 5cpf is ON HOLD Authors: Li, H.-J., Pan, P. Description: Compensation of the effect of isoleucine to alanine mutation by designed inhibition in the...

2015-07-29T13:41:02Z

New page: '''Unreleased structure''' The entry 5cpf is ON HOLD Authors: Li, H.-J., Pan, P. Description: Compensation of the effect of isoleucine to alanine mutation by designed inhibition in the...

New page

'''Unreleased structure'''

The entry 5cpf is ON HOLD

Authors: Li, H.-J., Pan, P.

Description: Compensation of the effect of isoleucine to alanine mutation by designed inhibition in the InhA enzyme
[[Category: Unreleased Structures]]
[[Category: Li, H.-J]]
[[Category: Pan, P]]