3s82 - Revision history

OCA at 12:49, 14 March 2024

2024-03-14T12:49:40Z

←Older revision		Revision as of 12:49, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3s82' size='340' side='right'caption='[[3s82]], [[Resolution\|resolution]] 1.73Å' scene=''>		<StructureSection load='3s82' size='340' side='right'caption='[[3s82]], [[Resolution\|resolution]] 1.73Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3s82]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Myca1 Myca1~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S82 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3s82]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_avium_104 Mycobacterium avium 104]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S82 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</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]] 1.73Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MAV_3382 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243243 MYCA1])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Methionine_adenosyltransferase Methionine adenosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.6 2.5.1.6] </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=3s82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s82 OCA], [https://pdbe.org/3s82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s82 RCSB], [https://www.ebi.ac.uk/pdbsum/3s82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s82 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=3s82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s82 OCA], [https://pdbe.org/3s82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s82 RCSB], [https://www.ebi.ac.uk/pdbsum/3s82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s82 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/METK_MYCA1 METK_MYCA1]] Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The overall synthetic reaction is composed of two sequential steps, AdoMet formation and the subsequent tripolyphosphate hydrolysis which occurs prior to release of AdoMet from the enzyme (By similarity).	+	[https://www.uniprot.org/uniprot/METK_MYCA1 METK_MYCA1] Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The overall synthetic reaction is composed of two sequential steps, AdoMet formation and the subsequent tripolyphosphate hydrolysis which occurs prior to release of AdoMet from the enzyme (By similarity).
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	High-resolution three-dimensional structures of essential Mycobacterium tuberculosis (Mtb) proteins provide templates for TB drug design, but are available for only a small fraction of the Mtb proteome. Here we evaluate an intra-genus "homolog-rescue" strategy to increase the structural information available for TB drug discovery by using mycobacterial homologs with conserved active sites. Of 179 potential TB drug targets selected for x-ray structure determination, only 16 yielded a crystal structure. By adding 1675 homologs from nine other mycobacterial species to the pipeline, structures representing an additional 52 otherwise intractable targets were solved. To determine whether these homolog structures would be useful surrogates in TB drug design, we compared the active sites of 106 pairs of Mtb and non-TB mycobacterial (NTM) enzyme homologs with experimentally determined structures, using three metrics of active site similarity, including superposition of continuous pharmacophoric property distributions. Pair-wise structural comparisons revealed that 19/22 pairs with >55% overall sequence identity had active site Calpha RMSD <1 A, >85% side chain identity, and >/=80% PSAPF (similarity based on pharmacophoric properties) indicating highly conserved active site shape and chemistry. Applying these results to the 52 NTM structures described above, 41 shared >55% sequence identity with the Mtb target, thus increasing the effective structural coverage of the 179 Mtb targets over three-fold (from 9% to 32%). The utility of these structures in TB drug design can be tested by designing inhibitors using the homolog structure and assaying the cognate Mtb enzyme; a promising test case, Mtb cytidylate kinase, is described. The homolog-rescue strategy evaluated here for TB is also generalizable to drug targets for other diseases.	+
-		+
-	Increasing the structural coverage of tuberculosis drug targets.,Baugh L, Phan I, Begley DW, Clifton MC, Armour B, Dranow DM, Taylor BM, Muruthi MM, Abendroth J, Fairman JW, Fox D 3rd, Dieterich SH, Staker BL, Gardberg AS, Choi R, Hewitt SN, Napuli AJ, Myers J, Barrett LK, Zhang Y, Ferrell M, Mundt E, Thompkins K, Tran N, Lyons-Abbott S, Abramov A, Sekar A, Serbzhinskiy D, Lorimer D, Buchko GW, Stacy R, Stewart LJ, Edwards TE, Van Voorhis WC, Myler PJ Tuberculosis (Edinb). 2014 Dec 19. pii: S1472-9792(14)20565-8. doi:, 10.1016/j.tube.2014.12.003. PMID:25613812<ref>PMID:25613812</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3s82" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
-	*[[Methionine adenosyltransferase\|Methionine adenosyltransferase]]
	*[[S-adenosylmethionine synthetase 3D structures\|S-adenosylmethionine synthetase 3D structures]]		*[[S-adenosylmethionine synthetase 3D structures\|S-adenosylmethionine synthetase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Methionine adenosyltransferase]]~~	+	[[Category: Mycobacterium avium 104]]
-	~~[[Category: Myca1~~]]	+
	[[Category: Structural genomic]]		[[Category: Structural genomic]]
-	[[Category: S-adenosylmethionine synthetase]]
-	[[Category: Ssgcid]]
-	[[Category: Transferase]]

OCA at 10:42, 22 June 2022

2022-06-22T10:42:04Z

←Older revision		Revision as of 10:42, 22 June 2022
Line 1:		Line 1:

	==Structure of a S-adenosylmethionine synthetase from Mycobacterium avium==		==Structure of a S-adenosylmethionine synthetase from Mycobacterium avium==
-	<StructureSection load='3s82' size='340' side='right' caption='[[3s82]], [[Resolution\|resolution]] 1.73Å' scene=''>	+	<StructureSection load='3s82' size='340' side='right'caption='[[3s82]], [[Resolution\|resolution]] 1.73Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3s82]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Myca1 Myca1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S82 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3S82 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3s82]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Myca1 Myca1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S82 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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MAV_3382 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243243 MYCA1])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MAV_3382 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243243 MYCA1])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Methionine_adenosyltransferase Methionine adenosyltransferase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.6 2.5.1.6] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Methionine_adenosyltransferase Methionine adenosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.6 2.5.1.6] </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=3s82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s82 OCA], [~~http~~://pdbe.org/3s82 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3s82 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3s82 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3s82 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=3s82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s82 OCA], [https://pdbe.org/3s82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s82 RCSB], [https://www.ebi.ac.uk/pdbsum/3s82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s82 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/METK_MYCA1 METK_MYCA1]] Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The overall synthetic reaction is composed of two sequential steps, AdoMet formation and the subsequent tripolyphosphate hydrolysis which occurs prior to release of AdoMet from the enzyme (By similarity).	+	[[https://www.uniprot.org/uniprot/METK_MYCA1 METK_MYCA1]] Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The overall synthetic reaction is composed of two sequential steps, AdoMet formation and the subsequent tripolyphosphate hydrolysis which occurs prior to release of AdoMet from the enzyme (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 3s82" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3s82" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Methionine adenosyltransferase\|Methionine adenosyltransferase]]
		+	*[[S-adenosylmethionine synthetase 3D structures\|S-adenosylmethionine synthetase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Methionine adenosyltransferase]]		[[Category: Methionine adenosyltransferase]]
	[[Category: Myca1]]		[[Category: Myca1]]

OCA at 18:35, 1 February 2017

2017-02-01T18:35:52Z

←Older revision		Revision as of 18:35, 1 February 2017
Line 1:		Line 1:
		+
	==Structure of a S-adenosylmethionine synthetase from Mycobacterium avium==		==Structure of a S-adenosylmethionine synthetase from Mycobacterium avium==
	<StructureSection load='3s82' size='340' side='right' caption='[[3s82]], [[Resolution\|resolution]] 1.73Å' scene=''>		<StructureSection load='3s82' size='340' side='right' caption='[[3s82]], [[Resolution\|resolution]] 1.73Å' scene=''>
Line 6:		Line 7:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MAV_3382 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243243 MYCA1])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MAV_3382 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243243 MYCA1])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionine_adenosyltransferase Methionine adenosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.6 2.5.1.6] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionine_adenosyltransferase Methionine adenosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.6 2.5.1.6] </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=3s82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s82 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3s82 RCSB], [http://www.ebi.ac.uk/pdbsum/3s82 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=3s82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s82 OCA], [http://pdbe.org/3s82 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3s82 RCSB], [http://www.ebi.ac.uk/pdbsum/3s82 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3s82 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 3s82" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:33, 22 April 2015

2015-04-22T06:33:23Z

←Older revision		Revision as of 06:33, 22 April 2015
Line 2:		Line 2:
	<StructureSection load='3s82' size='340' side='right' caption='[[3s82]], [[Resolution\|resolution]] 1.73Å' scene=''>		<StructureSection load='3s82' size='340' side='right' caption='[[3s82]], [[Resolution\|resolution]] 1.73Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3s82]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Mycobacterium_avium Mycobacterium avium~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S82 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3S82 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3s82]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myca1 Myca1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S82 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3S82 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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>		</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MAV_3382 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=~~1764 Mycobacterium avium~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MAV_3382 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243243 MYCA1])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionine_adenosyltransferase Methionine adenosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.6 2.5.1.6] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionine_adenosyltransferase Methionine adenosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.6 2.5.1.6] </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=3s82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s82 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3s82 RCSB], [http://www.ebi.ac.uk/pdbsum/3s82 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=3s82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s82 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3s82 RCSB], [http://www.ebi.ac.uk/pdbsum/3s82 PDBsum]</span></td></tr>
Line 10:		Line 10:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/METK_MYCA1 METK_MYCA1]] Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The overall synthetic reaction is composed of two sequential steps, AdoMet formation and the subsequent tripolyphosphate hydrolysis which occurs prior to release of AdoMet from the enzyme (By similarity).		[[http://www.uniprot.org/uniprot/METK_MYCA1 METK_MYCA1]] Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The overall synthetic reaction is composed of two sequential steps, AdoMet formation and the subsequent tripolyphosphate hydrolysis which occurs prior to release of AdoMet from the enzyme (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	High-resolution three-dimensional structures of essential Mycobacterium tuberculosis (Mtb) proteins provide templates for TB drug design, but are available for only a small fraction of the Mtb proteome. Here we evaluate an intra-genus "homolog-rescue" strategy to increase the structural information available for TB drug discovery by using mycobacterial homologs with conserved active sites. Of 179 potential TB drug targets selected for x-ray structure determination, only 16 yielded a crystal structure. By adding 1675 homologs from nine other mycobacterial species to the pipeline, structures representing an additional 52 otherwise intractable targets were solved. To determine whether these homolog structures would be useful surrogates in TB drug design, we compared the active sites of 106 pairs of Mtb and non-TB mycobacterial (NTM) enzyme homologs with experimentally determined structures, using three metrics of active site similarity, including superposition of continuous pharmacophoric property distributions. Pair-wise structural comparisons revealed that 19/22 pairs with >55% overall sequence identity had active site Calpha RMSD <1 A, >85% side chain identity, and >/=80% PSAPF (similarity based on pharmacophoric properties) indicating highly conserved active site shape and chemistry. Applying these results to the 52 NTM structures described above, 41 shared >55% sequence identity with the Mtb target, thus increasing the effective structural coverage of the 179 Mtb targets over three-fold (from 9% to 32%). The utility of these structures in TB drug design can be tested by designing inhibitors using the homolog structure and assaying the cognate Mtb enzyme; a promising test case, Mtb cytidylate kinase, is described. The homolog-rescue strategy evaluated here for TB is also generalizable to drug targets for other diseases.
		+
		+	Increasing the structural coverage of tuberculosis drug targets.,Baugh L, Phan I, Begley DW, Clifton MC, Armour B, Dranow DM, Taylor BM, Muruthi MM, Abendroth J, Fairman JW, Fox D 3rd, Dieterich SH, Staker BL, Gardberg AS, Choi R, Hewitt SN, Napuli AJ, Myers J, Barrett LK, Zhang Y, Ferrell M, Mundt E, Thompkins K, Tran N, Lyons-Abbott S, Abramov A, Sekar A, Serbzhinskiy D, Lorimer D, Buchko GW, Stacy R, Stewart LJ, Edwards TE, Van Voorhis WC, Myler PJ Tuberculosis (Edinb). 2014 Dec 19. pii: S1472-9792(14)20565-8. doi:, 10.1016/j.tube.2014.12.003. PMID:25613812<ref>PMID:25613812</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Methionine adenosyltransferase]]		[[Category: Methionine adenosyltransferase]]
-	[[Category: ~~Mycobacterium avium~~]]	+	[[Category: Myca1]]
	[[Category: Structural genomic]]		[[Category: Structural genomic]]
	[[Category: S-adenosylmethionine synthetase]]		[[Category: S-adenosylmethionine synthetase]]
	[[Category: Ssgcid]]		[[Category: Ssgcid]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 06:19, 25 December 2014

2014-12-25T06:19:22Z

←Older revision		Revision as of 06:19, 25 December 2014
Line 8:		Line 8:
	<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=3s82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s82 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3s82 RCSB], [http://www.ebi.ac.uk/pdbsum/3s82 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=3s82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s82 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3s82 RCSB], [http://www.ebi.ac.uk/pdbsum/3s82 PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/METK_MYCA1 METK_MYCA1]] Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The overall synthetic reaction is composed of two sequential steps, AdoMet formation and the subsequent tripolyphosphate hydrolysis which occurs prior to release of AdoMet from the enzyme (By similarity).
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 06:32, 21 December 2014

2014-12-21T06:32:35Z

←Older revision		Revision as of 06:32, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3s82\| PDB=3s82 \| SCENE= }}~~	+	==Structure of a S-adenosylmethionine synthetase from Mycobacterium avium==
-	===Structure of a S-adenosylmethionine synthetase from Mycobacterium avium===	+	<StructureSection load='3s82' size='340' side='right' caption='[[3s82]], [[Resolution\|resolution]] 1.73Å' scene=''>
-		+	== Structural highlights ==
-	==~~Function~~==	+	<table><tr><td colspan='2'>[[3s82]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_avium Mycobacterium avium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S82 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3S82 FirstGlance]. <br>
-	[[~~http://www.uniprot.org/uniprot/METK_MYCA1 METK_MYCA1~~]] ~~Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The overall synthetic reaction is composed of two sequential steps~~, ~~AdoMet formation and the subsequent tripolyphosphate hydrolysis which occurs prior to release of AdoMet from the enzyme (By similarity)~~.	+	</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>
-		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MAV_3382 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1764 Mycobacterium avium])</td></tr>
-	==~~About this Structure~~==	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionine_adenosyltransferase Methionine adenosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.6 2.5.1.6] </span></td></tr>
-	[[3s82]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_avium Mycobacterium avium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S82 OCA].	+	<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=3s82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s82 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3s82 RCSB], [http://www.ebi.ac.uk/pdbsum/3s82 PDBsum]</span></td></tr>
		+	</table>
		+	__TOC__
		+	</StructureSection>
	[[Category: Methionine adenosyltransferase]]		[[Category: Methionine adenosyltransferase]]
	[[Category: Mycobacterium avium]]		[[Category: Mycobacterium avium]]
-	[[Category: ~~Disease, Seattle~~ Structural ~~Genomics Center for Infectious.]]~~	+	[[Category: Structural genomic]]
-	~~[[Category: SSGCID, Seattle Structural Genomics Center for Infectious Disease.~~]]	+
	[[Category: S-adenosylmethionine synthetase]]		[[Category: S-adenosylmethionine synthetase]]
-	[[Category: Seattle structural genomics center for infectious disease]]
	[[Category: Ssgcid]]		[[Category: Ssgcid]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 07:44, 16 May 2013

2013-05-16T07:44:25Z

←Older revision		Revision as of 07:44, 16 May 2013
Line 1:		Line 1:
-	[[Image:3s82.jpg\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_3s82", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3s82\| PDB=3s82 \| SCENE= }}		{{STRUCTURE_3s82\| PDB=3s82 \| SCENE= }}
-
	===Structure of a S-adenosylmethionine synthetase from Mycobacterium avium===		===Structure of a S-adenosylmethionine synthetase from Mycobacterium avium===

		+	==Function==
		+	[[http://www.uniprot.org/uniprot/METK_MYCA1 METK_MYCA1]] Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The overall synthetic reaction is composed of two sequential steps, AdoMet formation and the subsequent tripolyphosphate hydrolysis which occurs prior to release of AdoMet from the enzyme (By similarity).

	==About this Structure==		==About this Structure==
Line 18:		Line 11:
	[[Category: Disease, Seattle Structural Genomics Center for Infectious.]]		[[Category: Disease, Seattle Structural Genomics Center for Infectious.]]
	[[Category: SSGCID, Seattle Structural Genomics Center for Infectious Disease.]]		[[Category: SSGCID, Seattle Structural Genomics Center for Infectious Disease.]]
		+	[[Category: S-adenosylmethionine synthetase]]
		+	[[Category: Seattle structural genomics center for infectious disease]]
		+	[[Category: Ssgcid]]
		+	[[Category: Transferase]]

OCA: Protected "3s82" [edit=sysop:move=sysop]

2011-06-08T05:25:59Z

Protected "3s82" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:25, 8 June 2011