3tde - Revision history

OCA at 13:25, 14 March 2024

OCA — Thu, 14 Mar 2024 13:25:12 GMT

←Older revision		Revision as of 13:25, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3tde' size='340' side='right'caption='[[3tde]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='3tde' size='340' side='right'caption='[[3tde]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tde]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus~~ tuberculosis~~" (zopf 1883) klein 1884~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TDE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TDE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tde]] is a 4 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=3TDE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TDE FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.85Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max~~-~~height: 3em;'>[[3rv2\|3rv2]]~~, [[~~3s82~~\|~~3s82~~]]~~</div>~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>metK, MT1437, MTCY21B4.09, Rv1392 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~1773~~ "~~Bacillus tuberculosis~~" ~~(Zopf 1883) Klein 1884])</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=3tde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tde OCA], [https://pdbe.org/3tde PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tde RCSB], [https://www.ebi.ac.uk/pdbsum/3tde PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tde 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=3tde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tde OCA], [https://pdbe.org/3tde PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tde RCSB], [https://www.ebi.ac.uk/pdbsum/3tde PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tde ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/METK_MYCTU METK_MYCTU]] 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_MYCTU METK_MYCTU] 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 3tde" 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 tuberculosis]]
-	~~[[Category: Structural genomic]]~~	+
-	~~[[Category: Adomet]]~~	+
-	~~[[Category: Sam]]~~	+
-	~~[[Category: Ssgcid]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Tuberculosis~~]]	+

OCA at 16:53, 6 July 2022

OCA — Wed, 06 Jul 2022 16:53:10 GMT

←Older revision		Revision as of 16:53, 6 July 2022
Line 1:		Line 1:

	==Crystal structure of S-adenosylmethionine synthetase Rv1392 from Mycobacterium tuberculosis==		==Crystal structure of S-adenosylmethionine synthetase Rv1392 from Mycobacterium tuberculosis==
-	<StructureSection load='3tde' size='340' side='right' caption='[[3tde]], [[Resolution\|resolution]] 1.85Å' scene=''>	+	<StructureSection load='3tde' size='340' side='right'caption='[[3tde]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tde]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TDE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3TDE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tde]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TDE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TDE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3rv2\|3rv2]], [[3s82\|3s82]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3rv2\|3rv2]], [[3s82\|3s82]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MT1437, MTCY21B4.09, Rv1392 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MT1437, MTCY21B4.09, Rv1392 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=3tde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tde OCA], [~~http~~://pdbe.org/3tde PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3tde RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3tde PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3tde 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=3tde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tde OCA], [https://pdbe.org/3tde PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tde RCSB], [https://www.ebi.ac.uk/pdbsum/3tde PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tde ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/METK_MYCTU METK_MYCTU]] 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_MYCTU METK_MYCTU]] 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 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 3tde" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3tde" 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: Structural genomic]]		[[Category: Structural genomic]]

OCA at 18:53, 1 February 2017

OCA — Wed, 01 Feb 2017 18:53:08 GMT

←Older revision		Revision as of 18:53, 1 February 2017
Line 1:		Line 1:
		+
	==Crystal structure of S-adenosylmethionine synthetase Rv1392 from Mycobacterium tuberculosis==		==Crystal structure of S-adenosylmethionine synthetase Rv1392 from Mycobacterium tuberculosis==
	<StructureSection load='3tde' size='340' side='right' caption='[[3tde]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='3tde' size='340' side='right' caption='[[3tde]], [[Resolution\|resolution]] 1.85Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MT1437, MTCY21B4.09, Rv1392 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MT1437, MTCY21B4.09, Rv1392 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=3tde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tde OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tde RCSB], [http://www.ebi.ac.uk/pdbsum/3tde 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=3tde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tde OCA], [http://pdbe.org/3tde PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tde RCSB], [http://www.ebi.ac.uk/pdbsum/3tde PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tde ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	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 3tde" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:28, 22 April 2015

OCA — Wed, 22 Apr 2015 07:28:14 GMT

←Older revision		Revision as of 07:28, 22 April 2015
Line 2:		Line 2:
	<StructureSection load='3tde' size='340' side='right' caption='[[3tde]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='3tde' size='340' side='right' caption='[[3tde]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tde]] is a 4 chain structure with sequence 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=3TDE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TDE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tde]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TDE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TDE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3rv2\|3rv2]], [[3s82\|3s82]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3rv2\|3rv2]], [[3s82\|3s82]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MT1437, MTCY21B4.09, Rv1392 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 ~~Mycobacterium~~ tuberculosis])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MT1437, MTCY21B4.09, Rv1392 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=3tde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tde OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tde RCSB], [http://www.ebi.ac.uk/pdbsum/3tde 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=3tde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tde OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tde RCSB], [http://www.ebi.ac.uk/pdbsum/3tde PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/METK_MYCTU METK_MYCTU]] 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 tuberculosis]]
	[[Category: Structural genomic]]		[[Category: Structural genomic]]
	[[Category: Adomet]]		[[Category: Adomet]]

OCA at 10:11, 4 January 2015

OCA — Sun, 04 Jan 2015 10:11:52 GMT

←Older revision		Revision as of 10:11, 4 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3tde]] is a 4 chain structure with sequence 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=3TDE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TDE FirstGlance]. <br>		<table><tr><td colspan='2'>[[3tde]] is a 4 chain structure with sequence 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=3TDE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TDE FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3rv2\|3rv2]], [[3s82\|3s82]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3rv2\|3rv2]], [[3s82\|3s82]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MT1437, MTCY21B4.09, Rv1392 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MT1437, MTCY21B4.09, Rv1392 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])</td></tr>
-	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tde OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tde RCSB], [http://www.ebi.ac.uk/pdbsum/3tde 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=3tde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tde OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tde RCSB], [http://www.ebi.ac.uk/pdbsum/3tde PDBsum]</span></td></tr>
-	<table>	+	</table>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Methionine adenosyltransferase]]		[[Category: Methionine adenosyltransferase]]
	[[Category: Mycobacterium tuberculosis]]		[[Category: Mycobacterium tuberculosis]]
-	[[Category: ~~SSGCID, Seattle~~ Structural ~~Genomics Center for Infectious Disease.~~]]	+	[[Category: Structural genomic]]
	[[Category: Adomet]]		[[Category: Adomet]]
	[[Category: Sam]]		[[Category: Sam]]
-	[[Category: Seattle structural genomics center for infectious disease]]
	[[Category: Ssgcid]]		[[Category: Ssgcid]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Tuberculosis]]		[[Category: Tuberculosis]]

OCA at 06:46, 5 June 2014

OCA — Thu, 05 Jun 2014 06:46:16 GMT

←Older revision		Revision as of 06:46, 5 June 2014
Line 1:		Line 1:
-	~~[[Image:3tde.jpg\|left\|200px]]~~	+	==Crystal structure of S-adenosylmethionine synthetase Rv1392 from Mycobacterium tuberculosis==
-		+	<StructureSection load='3tde' size='340' side='right' caption='[[3tde]], [[Resolution\|resolution]] 1.85Å' scene=''>
-	~~<!--~~	+	== Structural highlights ==
-	~~The line below this paragraph, containing "STRUCTURE_3tde", creates the "Structure Box" on the page.~~	+	<table><tr><td colspan='2'>[[3tde]] is a 4 chain structure with sequence 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=3TDE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TDE FirstGlance]. <br>
-	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~	+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene><br>
-	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~	+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3rv2\|3rv2]], [[3s82\|3s82]]</td></tr>
-	~~or leave the SCENE parameter empty for the default display.~~	+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">metK, MT1437, MTCY21B4.09, Rv1392 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])</td></tr>
-	~~-->~~	+	<tr><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>
-	~~{{STRUCTURE_3tde\| PDB=3tde \| SCENE= }}~~	+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tde OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tde RCSB], [http://www.ebi.ac.uk/pdbsum/3tde PDBsum]</span></td></tr>
-		+	<table>
-	===Crystal structure of S-adenosylmethionine synthetase Rv1392 from Mycobacterium tuberculosis===	+	__TOC__
-		+	</StructureSection>
-		+
-	==~~About this Structure~~==	+
-	[[3tde]] is a 4 chain structure with sequence 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=3TDE OCA].	+
	[[Category: Methionine adenosyltransferase]]		[[Category: Methionine adenosyltransferase]]
	[[Category: Mycobacterium tuberculosis]]		[[Category: Mycobacterium tuberculosis]]

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

OCA — Wed, 17 Aug 2011 06:36:09 GMT

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

←Older revision

Revision as of 06:36, 17 August 2011