4ele - Revision history

OCA at 15:04, 14 March 2024

2024-03-14T15:04:20Z

←Older revision		Revision as of 15:04, 14 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ele]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis_str._Sterne Bacillus anthracis str. Sterne]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ELE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ELE FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ele]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis_str._Sterne Bacillus anthracis str. Sterne]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ELE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ELE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=31I:(2E)-3-{5-[(2,4-DIAMINOPYRIMIDIN-5-YL)METHYL]-2,3-DIMETHOXYPHENYL}-1-[(1S)-1-(PROPAN-2-YL)PHTHALAZIN-2(1H)-YL]PROP-2-EN-1-ONE'>31I</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.35Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=31I:(2E)-3-{5-[(2,4-DIAMINOPYRIMIDIN-5-YL)METHYL]-2,3-DIMETHOXYPHENYL}-1-[(1S)-1-(PROPAN-2-YL)PHTHALAZIN-2(1H)-YL]PROP-2-EN-1-ONE'>31I</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=4ele FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ele OCA], [https://pdbe.org/4ele PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ele RCSB], [https://www.ebi.ac.uk/pdbsum/4ele PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ele 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=4ele FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ele OCA], [https://pdbe.org/4ele PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ele RCSB], [https://www.ebi.ac.uk/pdbsum/4ele PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ele ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/Q81R22_BACAN Q81R22_BACAN]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194]	+	[https://www.uniprot.org/uniprot/Q81R22_BACAN Q81R22_BACAN] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194]
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Background: Bacterial resistance to antibiotic therapies is increasing and new treatment options are badly needed. There is an overlap between these resistant bacteria and organisms classified as likely bioterror weapons. For example, Bacillus anthracis is innately resistant to the anti-folate trimethoprim due to sequence changes found in the dihydrofolate reductase enzyme. Development of new inhibitors provides an opportunity to enhance the current arsenal of anti-folate antibiotics while also expanding the coverage of the anti-folate class. Methods: We have characterized inhibitors of B. anthracis dihydrofolate reductase by measuring the K(i) and MIC values and calculating the energetics of binding. This series contains a core diaminopyrimidine ring, a central dimethoxybenzyl ring, and a dihydrophthalazine moiety. We have altered the chemical groups extended from a chiral center on the dihydropyridazine ring of the phthalazine moiety. The interactions for the most potent compounds were visualized by X-ray structure determination. Results: We find that the potency of individual enantiomers is divergent with clear preference for the S-enantiomer, while maintaining a high conservation of contacts within the binding site. The preference for enantiomers seems to be predicated largely by differential interactions with protein residues Leu29, Gln30 and Arg53. Conclusions: These studies have clarified the activity of modifications and of individual enantiomers, and highlighted the role of the less-active R-enantiomer in effectively diluting the more active S-enantiomer in racemic solutions. This directly contributes to the development of new antimicrobials, combating trimethoprim resistance, and treatment options for potential bioterrorism agents.	+
-		+
-	Structure-activity relationship for enantiomers of potent inhibitors of B. anthracis dihydrofolate reductase.,Bourne CR, Wakeham N, Nammalwar B, Tseitin V, Bourne PC, Barrow EW, Mylvaganam S, Ramnarayan K, Bunce RA, Berlin KD, Barrow WW Biochim Biophys Acta. 2013 Jan;1834(1):46-52. doi: 10.1016/j.bbapap.2012.09.001. , Epub 2012 Sep 20. PMID:22999981<ref>PMID:22999981</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4ele" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]		*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 07:16, 28 September 2022

2022-09-28T07:16:30Z

←Older revision		Revision as of 07:16, 28 September 2022
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	==Structure-activity relationship guides enantiomeric preference among potent inhibitors of B. anthracis dihydrofolate reductase==		==Structure-activity relationship guides enantiomeric preference among potent inhibitors of B. anthracis dihydrofolate reductase==
-	<StructureSection load='4ele' size='340' side='right' caption='[[4ele]], [[Resolution\|resolution]] 2.35Å' scene=''>	+	<StructureSection load='4ele' size='340' side='right'caption='[[4ele]], [[Resolution\|resolution]] 2.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ele]] is a 8 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Bacillus_anthracis_(strain_sterne)~~ Bacillus anthracis ~~(strain sterne)~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ELE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4ELE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ele]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis_str._Sterne Bacillus anthracis str. Sterne]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ELE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ELE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=31I:(2E)-3-{5-[(2,4-DIAMINOPYRIMIDIN-5-YL)METHYL]-2,3-DIMETHOXYPHENYL}-1-[(1S)-1-(PROPAN-2-YL)PHTHALAZIN-2(1H)-YL]PROP-2-EN-1-ONE'>31I</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=31I:(2E)-3-{5-[(2,4-DIAMINOPYRIMIDIN-5-YL)METHYL]-2,3-DIMETHOXYPHENYL}-1-[(1S)-1-(PROPAN-2-YL)PHTHALAZIN-2(1H)-YL]PROP-2-EN-1-ONE'>31I</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3fl8\|3fl8]], [[3fl9\|3fl9]], [[3elb\|3elb]], [[3elf\|3elf]], [[4elg\|4elg]], [[4elh\|4elh]]</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=4ele FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ele OCA], [https://pdbe.org/4ele PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ele RCSB], [https://www.ebi.ac.uk/pdbsum/4ele PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ele ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BAS2083, BA_2237, dfrA, DHFR, GBAA_2237 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=260799 Bacillus anthracis (strain Sterne)])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </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=4ele FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ele OCA], [~~http~~://pdbe.org/4ele PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ele RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ele PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ele ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/Q81R22_BACAN Q81R22_BACAN]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194]	+	[[https://www.uniprot.org/uniprot/Q81R22_BACAN Q81R22_BACAN]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 20:

	==See Also==		==See Also==
-	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]	+	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Dihydrofolate reductase~~]]	+	[[Category: Bacillus anthracis str. Sterne]]
-	[[Category: ~~Barrow, W W~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Bourne, C R~~]]	+	[[Category: Barrow WW]]
-	[[Category: ~~Oxidoreductase-oxidoreductase inhibitor complex~~]]	+	[[Category: Bourne CR]]

OCA at 02:38, 5 August 2016

2016-08-05T02:38:37Z

←Older revision		Revision as of 02:38, 5 August 2016
Line 1:		Line 1:
		+
	==Structure-activity relationship guides enantiomeric preference among potent inhibitors of B. anthracis dihydrofolate reductase==		==Structure-activity relationship guides enantiomeric preference among potent inhibitors of B. anthracis dihydrofolate reductase==
	<StructureSection load='4ele' size='340' side='right' caption='[[4ele]], [[Resolution\|resolution]] 2.35Å' scene=''>		<StructureSection load='4ele' size='340' side='right' caption='[[4ele]], [[Resolution\|resolution]] 2.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ele]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Bacillus_anthracis_str._sterne~~ Bacillus anthracis ~~str.~~ sterne]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ELE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ELE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ele]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis_(strain_sterne) Bacillus anthracis (strain sterne)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ELE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ELE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=31I:(2E)-3-{5-[(2,4-DIAMINOPYRIMIDIN-5-YL)METHYL]-2,3-DIMETHOXYPHENYL}-1-[(1S)-1-(PROPAN-2-YL)PHTHALAZIN-2(1H)-YL]PROP-2-EN-1-ONE'>31I</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=31I:(2E)-3-{5-[(2,4-DIAMINOPYRIMIDIN-5-YL)METHYL]-2,3-DIMETHOXYPHENYL}-1-[(1S)-1-(PROPAN-2-YL)PHTHALAZIN-2(1H)-YL]PROP-2-EN-1-ONE'>31I</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3fl8\|3fl8]], [[3fl9\|3fl9]], [[3elb\|3elb]], [[3elf\|3elf]], [[4elg\|4elg]], [[4elh\|4elh]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3fl8\|3fl8]], [[3fl9\|3fl9]], [[3elb\|3elb]], [[3elf\|3elf]], [[4elg\|4elg]], [[4elh\|4elh]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BAS2083, BA_2237, dfrA, DHFR, GBAA_2237 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=260799 Bacillus anthracis ~~str.~~ Sterne])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BAS2083, BA_2237, dfrA, DHFR, GBAA_2237 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=260799 Bacillus anthracis (strain Sterne)])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </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=4ele FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ele OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ele RCSB], [http://www.ebi.ac.uk/pdbsum/4ele 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=4ele FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ele OCA], [http://pdbe.org/4ele PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ele RCSB], [http://www.ebi.ac.uk/pdbsum/4ele PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ele 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 4ele" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Bacillus anthracis str. sterne]]
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Barrow, W W]]		[[Category: Barrow, W W]]
	[[Category: Bourne, C R]]		[[Category: Bourne, C R]]
	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]		[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 22:05, 24 December 2014

2014-12-24T22:05:55Z

←Older revision		Revision as of 22:05, 24 December 2014
Line 9:		Line 9:
	<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=4ele FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ele OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ele RCSB], [http://www.ebi.ac.uk/pdbsum/4ele 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=4ele FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ele OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ele RCSB], [http://www.ebi.ac.uk/pdbsum/4ele PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/Q81R22_BACAN Q81R22_BACAN]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 14:25, 9 December 2014

2014-12-09T14:25:29Z

←Older revision		Revision as of 14:25, 9 December 2014
Line 1:		Line 1:
-	[[~~Image:~~4ele.~~jpg~~\|~~left~~\|~~200px~~]]	+	==Structure-activity relationship guides enantiomeric preference among potent inhibitors of B. anthracis dihydrofolate reductase==
		+	<StructureSection load='4ele' size='340' side='right' caption='[[4ele]], [[Resolution\|resolution]] 2.35Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4ele]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis_str._sterne Bacillus anthracis str. sterne]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ELE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ELE FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=31I:(2E)-3-{5-[(2,4-DIAMINOPYRIMIDIN-5-YL)METHYL]-2,3-DIMETHOXYPHENYL}-1-[(1S)-1-(PROPAN-2-YL)PHTHALAZIN-2(1H)-YL]PROP-2-EN-1-ONE'>31I</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3fl8\|3fl8]], [[3fl9\|3fl9]], [[3elb\|3elb]], [[3elf\|3elf]], [[4elg\|4elg]], [[4elh\|4elh]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BAS2083, BA_2237, dfrA, DHFR, GBAA_2237 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=260799 Bacillus anthracis str. Sterne])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </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=4ele FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ele OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ele RCSB], [http://www.ebi.ac.uk/pdbsum/4ele PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Background: Bacterial resistance to antibiotic therapies is increasing and new treatment options are badly needed. There is an overlap between these resistant bacteria and organisms classified as likely bioterror weapons. For example, Bacillus anthracis is innately resistant to the anti-folate trimethoprim due to sequence changes found in the dihydrofolate reductase enzyme. Development of new inhibitors provides an opportunity to enhance the current arsenal of anti-folate antibiotics while also expanding the coverage of the anti-folate class. Methods: We have characterized inhibitors of B. anthracis dihydrofolate reductase by measuring the K(i) and MIC values and calculating the energetics of binding. This series contains a core diaminopyrimidine ring, a central dimethoxybenzyl ring, and a dihydrophthalazine moiety. We have altered the chemical groups extended from a chiral center on the dihydropyridazine ring of the phthalazine moiety. The interactions for the most potent compounds were visualized by X-ray structure determination. Results: We find that the potency of individual enantiomers is divergent with clear preference for the S-enantiomer, while maintaining a high conservation of contacts within the binding site. The preference for enantiomers seems to be predicated largely by differential interactions with protein residues Leu29, Gln30 and Arg53. Conclusions: These studies have clarified the activity of modifications and of individual enantiomers, and highlighted the role of the less-active R-enantiomer in effectively diluting the more active S-enantiomer in racemic solutions. This directly contributes to the development of new antimicrobials, combating trimethoprim resistance, and treatment options for potential bioterrorism agents.

-	~~{{STRUCTURE_4ele\| PDB=4ele \| SCENE= }}~~	+	Structure-activity relationship for enantiomers of potent inhibitors of B. anthracis dihydrofolate reductase.,Bourne CR, Wakeham N, Nammalwar B, Tseitin V, Bourne PC, Barrow EW, Mylvaganam S, Ramnarayan K, Bunce RA, Berlin KD, Barrow WW Biochim Biophys Acta. 2013 Jan;1834(1):46-52. doi: 10.1016/j.bbapap.2012.09.001. , Epub 2012 Sep 20. PMID:22999981<ref>PMID:22999981</ref>

-	~~===Structure-activity relationship guides enantiomeric preference among potent inhibitors~~ of B. ~~anthracis dihydrofolate reductase===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-	~~{{ABSTRACT_PUBMED_22999981}}~~	+	==See Also==
-		+	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]
-	==~~About this Structure~~==	+	== References ==
-	[[~~4ele~~]] ~~is a 8 chain structure with sequence from [http:~~//~~en.wikipedia.org/wiki/Bacillus_anthracis_str._sterne Bacillus anthracis str. sterne]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ELE OCA].~~	+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Bacillus anthracis str. sterne]]		[[Category: Bacillus anthracis str. sterne]]
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
-	[[Category: Barrow, W W.]]	+	[[Category: Barrow, W W]]
-	[[Category: Bourne, C R~~.]]~~	+	[[Category: Bourne, C R]]
-	~~[[Category: Dihydrofolate reductase~~]]	+
	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]		[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 10:29, 13 February 2013

2013-02-13T10:29:20Z

←Older revision		Revision as of 10:29, 13 February 2013
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-	~~'''Unreleased structure'''~~	+	[[Image:4ele.jpg\|left\|200px]]

-	~~The entry~~ 4ele ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4ele\| PDB=4ele \| SCENE= }}

-	~~Authors: Bourne, C.R., Barrow, W.W~~.	+	===Structure-activity relationship guides enantiomeric preference among potent inhibitors of B. anthracis dihydrofolate reductase===

-	~~Description:~~ Structure-~~activity relationship guides enantiomeric preference among potent inhibitors of B~~. anthracis ~~dihydrofolate~~ reductase	+	{{ABSTRACT_PUBMED_22999981}}
		+
		+	==About this Structure==
		+	[[4ele]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis_str._sterne Bacillus anthracis str. sterne]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ELE OCA].
		+	[[Category: Bacillus anthracis str. sterne]]
		+	[[Category: Dihydrofolate reductase]]
		+	[[Category: Barrow, W W.]]
		+	[[Category: Bourne, C R.]]
		+	[[Category: Dihydrofolate reductase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 08:54, 25 April 2012

2012-04-25T08:54:13Z

←Older revision		Revision as of 08:54, 25 April 2012
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4ele is ON HOLD	+	The entry 4ele is ON HOLD until Paper Publication

	Authors: Bourne, C.R., Barrow, W.W.		Authors: Bourne, C.R., Barrow, W.W.

	Description: Structure-activity relationship guides enantiomeric preference among potent inhibitors of B. anthracis dihydrofolate reductase		Description: Structure-activity relationship guides enantiomeric preference among potent inhibitors of B. anthracis dihydrofolate reductase

OCA: Protected "4ele" [edit=sysop:move=sysop]

2012-04-18T07:34:36Z

Protected "4ele" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:34, 18 April 2012

OCA: New page: '''Unreleased structure''' The entry 4ele is ON HOLD Authors: Bourne, C.R., Barrow, W.W. Description: Structure-activity relationship guides enantiomeric preference among potent inhibi...

2012-04-18T07:34:35Z

New page: '''Unreleased structure''' The entry 4ele is ON HOLD Authors: Bourne, C.R., Barrow, W.W. Description: Structure-activity relationship guides enantiomeric preference among potent inhibi...

New page

'''Unreleased structure'''

The entry 4ele is ON HOLD

Authors: Bourne, C.R., Barrow, W.W.

Description: Structure-activity relationship guides enantiomeric preference among potent inhibitors of B. anthracis dihydrofolate reductase