4h8e - Revision history

OCA at 11:36, 1 March 2024

OCA — Fri, 01 Mar 2024 11:36:03 GMT

←Older revision		Revision as of 11:36, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4h8e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_N315 Staphylococcus aureus subsp. aureus N315]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H8E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H8E FirstGlance]. <br>		<table><tr><td colspan='2'>[[4h8e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_N315 Staphylococcus aureus subsp. aureus N315]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H8E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H8E FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.3Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4h8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h8e OCA], [https://pdbe.org/4h8e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h8e RCSB], [https://www.ebi.ac.uk/pdbsum/4h8e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h8e 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=4h8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h8e OCA], [https://pdbe.org/4h8e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h8e RCSB], [https://www.ebi.ac.uk/pdbsum/4h8e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h8e ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/ISPT_STAAN ISPT_STAAN] Catalyzes the condensation of isopentenyl diphosphate (IPP) with allylic pyrophosphates generating different type of terpenoids.[HAMAP-Rule:MF_01139]		[https://www.uniprot.org/uniprot/ISPT_STAAN ISPT_STAAN] Catalyzes the condensation of isopentenyl diphosphate (IPP) with allylic pyrophosphates generating different type of terpenoids.[HAMAP-Rule:MF_01139]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	With the rise in resistance to antibiotics such as methicillin, there is a need for new drugs. We report here the discovery and X-ray crystallographic structures of 10 chemically diverse compounds (benzoic, diketo, and phosphonic acids, as well as a bisamidine and a bisamine) that inhibit bacterial undecaprenyl diphosphate synthase, an essential enzyme involved in cell wall biosynthesis. The inhibitors bind to one or more of the four undecaprenyl diphosphate synthase inhibitor binding sites identified previously, with the most active leads binding to site 4, outside the catalytic center. The most potent leads are active against Staphylococcus aureus [minimal inhibitory concentration (MIC)(90) approximately 0.25 microg/mL], and one potently synergizes with methicillin (fractional inhibitory concentration index = 0.25) and is protective in a mouse infection model. These results provide numerous leads for antibacterial development and open up the possibility of restoring sensitivity to drugs such as methicillin, using combination therapies.
-
-	Antibacterial drug leads targeting isoprenoid biosynthesis.,Zhu W, Zhang Y, Sinko W, Hensler ME, Olson J, Molohon KJ, Lindert S, Cao R, Li K, Wang K, Wang Y, Liu YL, Sankovsky A, de Oliveira CA, Mitchell DA, Nizet V, McCammon JA, Oldfield E Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):123-8. doi: 10.1073/pnas.1219899110. , Epub 2012 Dec 17. PMID:23248302<ref>PMID:23248302</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4h8e" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Undecaprenyl pyrophosphate synthase\|Undecaprenyl pyrophosphate synthase]]		*[[Undecaprenyl pyrophosphate synthase\|Undecaprenyl pyrophosphate synthase]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 08:04, 3 November 2022

OCA — Thu, 03 Nov 2022 08:04:48 GMT

←Older revision		Revision as of 08:04, 3 November 2022
Line 1:		Line 1:

	==Structure of S. aureus undecaprenyl diphosphate synthase in complex with FPP and sulfate==		==Structure of S. aureus undecaprenyl diphosphate synthase in complex with FPP and sulfate==
-	<StructureSection load='4h8e' size='340' side='right' caption='[[4h8e]], [[Resolution\|resolution]] 1.30Å' scene=''>	+	<StructureSection load='4h8e' size='340' side='right'caption='[[4h8e]], [[Resolution\|resolution]] 1.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4h8e]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Staan Staan~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H8E OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4H8E FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4h8e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_N315 Staphylococcus aureus subsp. aureus N315]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H8E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H8E FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4h2j\|4h2j]], [[4h2m\|4h2m]], [[4h2o\|4h2o]], [[4h38\|4h38]], [[4h3a\|4h3a]], [[4h3c\|4h3c]]</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=4h8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h8e OCA], [https://pdbe.org/4h8e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h8e RCSB], [https://www.ebi.ac.uk/pdbsum/4h8e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h8e ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">uppS, SA1103 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=158879 STAAN])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ditrans,polycis-undecaprenyl-diphosphate_synthase_((2E,6E)-farnesyl-_diphosphate_specific) Ditrans,polycis-undecaprenyl-diphosphate synthase ((2E,6E)-farnesyl- diphosphate specific)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.31 2.5.1.31] </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=4h8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h8e OCA], [~~http~~://pdbe.org/4h8e PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4h8e RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4h8e PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4h8e ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ISPT_STAAN ISPT_STAAN]] Catalyzes the condensation of isopentenyl diphosphate (IPP) with allylic pyrophosphates generating different type of terpenoids.[HAMAP-Rule:MF_01139]	+	[https://www.uniprot.org/uniprot/ISPT_STAAN ISPT_STAAN] Catalyzes the condensation of isopentenyl diphosphate (IPP) with allylic pyrophosphates generating different type of terpenoids.[HAMAP-Rule:MF_01139]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Staan~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Oldfield, E~~]]	+	[[Category: Staphylococcus aureus subsp. aureus N315]]
-	[[Category: ~~Zhu, W~~]]	+	[[Category: Oldfield E]]
-	[[Category: ~~Alpha-helix]]~~	+	[[Category: Zhu W]]
-	~~[[Category: Cell wall biosynthesis]]~~	+
-	~~[[Category: Farnesyl diphosphate binding]]~~	+
-	~~[[Category: Isopentenyl diphosphate binding]]~~	+
-	~~[[Category: Prenyl transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 17:53, 5 August 2016

OCA — Fri, 05 Aug 2016 17:53:23 GMT

←Older revision		Revision as of 17:53, 5 August 2016
Line 1:		Line 1:
-	[[Image:4h8e.png\|left\|200px]]

-	~~{{STRUCTURE_4h8e~~\| ~~PDB~~=4h8e \| ~~SCENE~~= }}	+	==Structure of S. aureus undecaprenyl diphosphate synthase in complex with FPP and sulfate==
		+	<StructureSection load='4h8e' size='340' side='right' caption='[[4h8e]], [[Resolution\|resolution]] 1.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4h8e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Staan Staan]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H8E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4H8E FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4h2j\|4h2j]], [[4h2m\|4h2m]], [[4h2o\|4h2o]], [[4h38\|4h38]], [[4h3a\|4h3a]], [[4h3c\|4h3c]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">uppS, SA1103 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=158879 STAAN])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ditrans,polycis-undecaprenyl-diphosphate_synthase_((2E,6E)-farnesyl-_diphosphate_specific) Ditrans,polycis-undecaprenyl-diphosphate synthase ((2E,6E)-farnesyl- diphosphate specific)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.31 2.5.1.31] </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=4h8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h8e OCA], [http://pdbe.org/4h8e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4h8e RCSB], [http://www.ebi.ac.uk/pdbsum/4h8e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4h8e ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ISPT_STAAN ISPT_STAAN]] Catalyzes the condensation of isopentenyl diphosphate (IPP) with allylic pyrophosphates generating different type of terpenoids.[HAMAP-Rule:MF_01139]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	With the rise in resistance to antibiotics such as methicillin, there is a need for new drugs. We report here the discovery and X-ray crystallographic structures of 10 chemically diverse compounds (benzoic, diketo, and phosphonic acids, as well as a bisamidine and a bisamine) that inhibit bacterial undecaprenyl diphosphate synthase, an essential enzyme involved in cell wall biosynthesis. The inhibitors bind to one or more of the four undecaprenyl diphosphate synthase inhibitor binding sites identified previously, with the most active leads binding to site 4, outside the catalytic center. The most potent leads are active against Staphylococcus aureus [minimal inhibitory concentration (MIC)(90) approximately 0.25 microg/mL], and one potently synergizes with methicillin (fractional inhibitory concentration index = 0.25) and is protective in a mouse infection model. These results provide numerous leads for antibacterial development and open up the possibility of restoring sensitivity to drugs such as methicillin, using combination therapies.

-	~~===Structure of~~ S. ~~aureus undecaprenyl diphosphate synthase in complex with FPP and sulfate===~~	+	Antibacterial drug leads targeting isoprenoid biosynthesis.,Zhu W, Zhang Y, Sinko W, Hensler ME, Olson J, Molohon KJ, Lindert S, Cao R, Li K, Wang K, Wang Y, Liu YL, Sankovsky A, de Oliveira CA, Mitchell DA, Nizet V, McCammon JA, Oldfield E Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):123-8. doi: 10.1073/pnas.1219899110. , Epub 2012 Dec 17. PMID:23248302<ref>PMID:23248302</ref>

-	~~{{ABSTRACT_PUBMED_23248302}}~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 4h8e" style="background-color:#fffaf0;"></div>

-	==~~About this Structure~~==	+	==See Also==
-	[[~~4h8e~~]] ~~is a 1 chain structure with sequence from [http:~~//en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_n315 Staphylococcus aureus subsp. aureus n315]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H8E OCA].	+	*[[Undecaprenyl pyrophosphate synthase\|Undecaprenyl pyrophosphate synthase]]
-	~~[[Category: Di-trans,poly-cis-decaprenylcistransferase]]~~	+	== References ==
-	[[Category: ~~Staphylococcus aureus subsp. aureus n315~~]]	+	<references/>
-	[[Category: Oldfield, E.]]	+	__TOC__
-	[[Category: Zhu, W.]]	+	</StructureSection>
		+	[[Category: Staan]]
		+	[[Category: Oldfield, E]]
		+	[[Category: Zhu, W]]
	[[Category: Alpha-helix]]		[[Category: Alpha-helix]]
	[[Category: Cell wall biosynthesis]]		[[Category: Cell wall biosynthesis]]

OCA at 08:08, 9 January 2013

OCA — Wed, 09 Jan 2013 08:08:03 GMT

←Older revision		Revision as of 08:08, 9 January 2013
Line 1:		Line 1:
-	[[Image:4h8e.~~jpg~~\|left\|200px]]	+	[[Image:4h8e.png\|left\|200px]]

	{{STRUCTURE_4h8e\| PDB=4h8e \| SCENE= }}		{{STRUCTURE_4h8e\| PDB=4h8e \| SCENE= }}
Line 5:		Line 5:
	===Structure of S. aureus undecaprenyl diphosphate synthase in complex with FPP and sulfate===		===Structure of S. aureus undecaprenyl diphosphate synthase in complex with FPP and sulfate===

		+	{{ABSTRACT_PUBMED_23248302}}

	==About this Structure==		==About this Structure==

OCA at 11:38, 19 December 2012

OCA — Wed, 19 Dec 2012 11:38:12 GMT

←Older revision		Revision as of 11:38, 19 December 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4h8e.jpg\|left\|200px]]

-	~~The entry~~ 4h8e ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4h8e\| PDB=4h8e \| SCENE= }}

-	~~Authors: Zhu, W., Oldfield, E~~.	+	===Structure of S. aureus undecaprenyl diphosphate synthase in complex with FPP and sulfate===

-	~~Description:~~ Structure ~~of S~~. aureus ~~undecaprenyl~~ diphosphate ~~synthase in~~ complex ~~with FPP and sulfate~~	+
		+	==About this Structure==
		+	[[4h8e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_n315 Staphylococcus aureus subsp. aureus n315]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H8E OCA].
		+	[[Category: Di-trans,poly-cis-decaprenylcistransferase]]
		+	[[Category: Staphylococcus aureus subsp. aureus n315]]
		+	[[Category: Oldfield, E.]]
		+	[[Category: Zhu, W.]]
		+	[[Category: Alpha-helix]]
		+	[[Category: Cell wall biosynthesis]]
		+	[[Category: Farnesyl diphosphate binding]]
		+	[[Category: Isopentenyl diphosphate binding]]
		+	[[Category: Prenyl transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 06:57, 10 October 2012

OCA — Wed, 10 Oct 2012 06:57:11 GMT

←Older revision		Revision as of 06:57, 10 October 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4h8e is ON HOLD	+	The entry 4h8e is ON HOLD until Paper Publication

	Authors: Zhu, W., Oldfield, E.		Authors: Zhu, W., Oldfield, E.

	Description: Structure of S. aureus undecaprenyl diphosphate synthase in complex with FPP and sulfate		Description: Structure of S. aureus undecaprenyl diphosphate synthase in complex with FPP and sulfate

OCA: Protected "4h8e" [edit=sysop:move=sysop]

OCA — Wed, 03 Oct 2012 05:49:25 GMT

Protected "4h8e" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:49, 3 October 2012

OCA: New page: '''Unreleased structure''' The entry 4h8e is ON HOLD Authors: Zhu, W., Oldfield, E. Description: Structure of S. aureus undecaprenyl diphosphate synthase in complex with FPP and sulfat...

OCA — Wed, 03 Oct 2012 05:49:23 GMT

New page: '''Unreleased structure''' The entry 4h8e is ON HOLD Authors: Zhu, W., Oldfield, E. Description: Structure of S. aureus undecaprenyl diphosphate synthase in complex with FPP and sulfat...

New page

'''Unreleased structure'''

The entry 4h8e is ON HOLD

Authors: Zhu, W., Oldfield, E.

Description: Structure of S. aureus undecaprenyl diphosphate synthase in complex with FPP and sulfate