6mkh - Revision history

OCA at 07:06, 3 April 2024

2024-04-03T07:06:39Z

←Older revision		Revision as of 07:06, 3 April 2024
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	<StructureSection load='6mkh' size='340' side='right'caption='[[6mkh]], [[Resolution\|resolution]] 2.62Å' scene=''>		<StructureSection load='6mkh' size='340' side='right'caption='[[6mkh]], [[Resolution\|resolution]] 2.62Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6mkh]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"enterococcus_proteiformis"_thiercelin_and_jouhaud_1903 "enterococcus proteiformis" thiercelin and jouhaud 1903~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MKH OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6MKH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6mkh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MKH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MKH FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IM2:(5R)-5-[(1S,2R)-1-FORMYL-2-HYDROXYPROPYL]-3-[(2-{[(E)-IMINOMETHYL]AMINO}ETHYL)SULFANYL]-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>IM2</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.62Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">pbp4, A6B47_10405, DAI13_12160 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1351 "Enterococcus proteiformis" Thiercelin and Jouhaud 1903])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IM2:(5R)-5-[(1S,2R)-1-FORMYL-2-HYDROXYPROPYL]-3-[(2-{[(E)-IMINOMETHYL]AMINO}ETHYL)SULFANYL]-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>IM2</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=6mkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mkh OCA], [~~http~~://pdbe.org/6mkh PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6mkh RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6mkh PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6mkh 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=6mkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mkh OCA], [https://pdbe.org/6mkh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mkh RCSB], [https://www.ebi.ac.uk/pdbsum/6mkh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mkh ProSAT]</span></td></tr>
	</table>		</table>
-	~~<div style~~=~~"background-color:#fffaf0;">~~	+	== Function ==
-	=~~= Publication Abstract from PubMed~~ ==	+	[https://www.uniprot.org/uniprot/Q9K3C9_ENTFL Q9K3C9_ENTFL]
-	The final steps of cell-wall biosynthesis in bacteria are carried out by penicillin-binding proteins (PBPs), whose transpeptidase domains form the crosslinks in peptidoglycan chains that define the bacterial cell wall. These enzymes are the targets of beta-lactam antibiotics, as their inhibition reduces the structural integrity of the cell wall. Bacterial resistance to antibiotics is a rapidly growing concern; however, the structural underpinnings of PBP-derived antibiotic resistance are poorly understood. PBP4 and PBP5 are low-affinity, class B transpeptidases that confer antibiotic resistance to Enterococcus faecalis and Enterococcus faecium, respectively. Here, we report the crystal structures of PBP4 (1.8 A) and PBP5 (2.7 A) in their apo and acyl-enzyme complexes with the beta-lactams benzylpenicillin, imipenem and ceftaroline. We found that, although these three beta-lactams adopt geometries similar to those observed in other class B PBP structures, there are small, but significant differences that likely decrease antibiotic efficacy. Further, we also discovered that the N-terminal domain extensions in this class of PBPs undergo large rigid-body rotations without impacting the structure of the catalytic transpeptidase domain. Together, our findings are defining the subtle functional and structural differences in the enterococcus PBPs that allow them to support transpeptidase activity while also conferring bacterial resistance to antibiotics that function as substrate mimics.	+
-		+
-	The structures of penicillin binding protein 4 (PBP4) and PBP5 from Enterococci provide structural insights into beta-lactam resistance.,Moon TM, D'Andrea ED, Lee CW, Soares A, Jakoncic J, Desbonnet C, Solache MG, Rice LB, Page R, Peti W J Biol Chem. 2018 Oct 24. pii: ~~RA118.006052. doi: 10.1074~~/~~jbc.RA118.006052. PMID:30355734<ref>PMID:30355734<~~/~~ref>~~	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U~~.S. ~~National Library of Medicine.<br>~~	+
-	</~~div>~~	+
-	~~<div class="pdbe-citations 6mkh" style="background-color:#fffaf0;"><~~/~~div>~~	+

	==See Also==		==See Also==
	*[[Penicillin-binding protein 3D structures\|Penicillin-binding protein 3D structures]]		*[[Penicillin-binding protein 3D structures\|Penicillin-binding protein 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Enterococcus ~~proteiformis thiercelin and jouhaud 1903~~]]	+	[[Category: Enterococcus faecalis]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Andrea~~, E D.D~~]]	+	[[Category: D'Andrea ED]]
-	[[Category: Moon~~, T M~~]]	+	[[Category: Moon TM]]
-	[[Category: Page, R]]	+	[[Category: Page R]]
-	[[Category: Peti, W]]	+	[[Category: Peti W]]
-	~~[[Category: Antibiotic]]~~	+
-	~~[[Category: Imipenem]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Pbp]]~~	+
-	~~[[Category: Penicillin-binding protein]]~~	+
-	~~[[Category: Protein binding-antibiotic complex~~]]	+

OCA at 10:58, 18 December 2019

2019-12-18T10:58:59Z

←Older revision		Revision as of 10:58, 18 December 2019
Line 1:		Line 1:

	==Crystal structure of pencillin binding protein 4 (PBP4) from Enterococcus faecalis in the imipenem-bound form==		==Crystal structure of pencillin binding protein 4 (PBP4) from Enterococcus faecalis in the imipenem-bound form==
-	<StructureSection load='6mkh' size='340' side='right' caption='[[6mkh]], [[Resolution\|resolution]] 2.62Å' scene=''>	+	<StructureSection load='6mkh' size='340' side='right'caption='[[6mkh]], [[Resolution\|resolution]] 2.62Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6mkh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"enterococcus_proteiformis"_thiercelin_and_jouhaud_1903 "enterococcus proteiformis" thiercelin and jouhaud 1903]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MKH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MKH FirstGlance]. <br>		<table><tr><td colspan='2'>[[6mkh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"enterococcus_proteiformis"_thiercelin_and_jouhaud_1903 "enterococcus proteiformis" thiercelin and jouhaud 1903]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MKH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MKH FirstGlance]. <br>
Line 17:		Line 17:
	</div>		</div>
	<div class="pdbe-citations 6mkh" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6mkh" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Penicillin-binding protein 3D structures\|Penicillin-binding protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 22:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Enterococcus proteiformis thiercelin and jouhaud 1903]]		[[Category: Enterococcus proteiformis thiercelin and jouhaud 1903]]
		+	[[Category: Large Structures]]
	[[Category: Andrea, E D.D]]		[[Category: Andrea, E D.D]]
	[[Category: Moon, T M]]		[[Category: Moon, T M]]

OCA at 12:55, 7 November 2018

2018-11-07T12:55:13Z

←Older revision		Revision as of 12:55, 7 November 2018
Line 3:		Line 3:
	<StructureSection load='6mkh' size='340' side='right' caption='[[6mkh]], [[Resolution\|resolution]] 2.62Å' scene=''>		<StructureSection load='6mkh' size='340' side='right' caption='[[6mkh]], [[Resolution\|resolution]] 2.62Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6mkh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MKH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MKH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6mkh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"enterococcus_proteiformis"_thiercelin_and_jouhaud_1903 "enterococcus proteiformis" thiercelin and jouhaud 1903]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MKH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MKH FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IM2:(5R)-5-[(1S,2R)-1-FORMYL-2-HYDROXYPROPYL]-3-[(2-{[(E)-IMINOMETHYL]AMINO}ETHYL)SULFANYL]-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>IM2</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IM2:(5R)-5-[(1S,2R)-1-FORMYL-2-HYDROXYPROPYL]-3-[(2-{[(E)-IMINOMETHYL]AMINO}ETHYL)SULFANYL]-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>IM2</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">pbp4, A6B47_10405, DAI13_12160 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1351 "Enterococcus proteiformis" Thiercelin and Jouhaud 1903])</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=6mkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mkh OCA], [http://pdbe.org/6mkh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mkh RCSB], [http://www.ebi.ac.uk/pdbsum/6mkh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mkh ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6mkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mkh OCA], [http://pdbe.org/6mkh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mkh RCSB], [http://www.ebi.ac.uk/pdbsum/6mkh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mkh ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The final steps of cell-wall biosynthesis in bacteria are carried out by penicillin-binding proteins (PBPs), whose transpeptidase domains form the crosslinks in peptidoglycan chains that define the bacterial cell wall. These enzymes are the targets of beta-lactam antibiotics, as their inhibition reduces the structural integrity of the cell wall. Bacterial resistance to antibiotics is a rapidly growing concern; however, the structural underpinnings of PBP-derived antibiotic resistance are poorly understood. PBP4 and PBP5 are low-affinity, class B transpeptidases that confer antibiotic resistance to Enterococcus faecalis and Enterococcus faecium, respectively. Here, we report the crystal structures of PBP4 (1.8 A) and PBP5 (2.7 A) in their apo and acyl-enzyme complexes with the beta-lactams benzylpenicillin, imipenem and ceftaroline. We found that, although these three beta-lactams adopt geometries similar to those observed in other class B PBP structures, there are small, but significant differences that likely decrease antibiotic efficacy. Further, we also discovered that the N-terminal domain extensions in this class of PBPs undergo large rigid-body rotations without impacting the structure of the catalytic transpeptidase domain. Together, our findings are defining the subtle functional and structural differences in the enterococcus PBPs that allow them to support transpeptidase activity while also conferring bacterial resistance to antibiotics that function as substrate mimics.
		+
		+	The structures of penicillin binding protein 4 (PBP4) and PBP5 from Enterococci provide structural insights into beta-lactam resistance.,Moon TM, D'Andrea ED, Lee CW, Soares A, Jakoncic J, Desbonnet C, Solache MG, Rice LB, Page R, Peti W J Biol Chem. 2018 Oct 24. pii: RA118.006052. doi: 10.1074/jbc.RA118.006052. PMID:30355734<ref>PMID:30355734</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6mkh" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Enterococcus proteiformis thiercelin and jouhaud 1903]]
	[[Category: Andrea, E D.D]]		[[Category: Andrea, E D.D]]
	[[Category: Moon, T M]]		[[Category: Moon, T M]]

OCA at 07:00, 31 October 2018

2018-10-31T07:00:58Z

←Older revision		Revision as of 07:00, 31 October 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6mkh is ON HOLD until Paper Publication~~	+	==Crystal structure of pencillin binding protein 4 (PBP4) from Enterococcus faecalis in the imipenem-bound form==
-		+	<StructureSection load='6mkh' size='340' side='right' caption='[[6mkh]], [[Resolution\|resolution]] 2.62Å' scene=''>
-	~~Authors: D'Andrea, E.D., Moon, T.M., Peti, W., Page, R.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6mkh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MKH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MKH FirstGlance]. <br>
-	~~Description:~~ Crystal structure of pencillin binding protein 4 (PBP4) from Enterococcus faecalis in the imipenem-bound form	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IM2:(5R)-5-[(1S,2R)-1-FORMYL-2-HYDROXYPROPYL]-3-[(2-{[(E)-IMINOMETHYL]AMINO}ETHYL)SULFANYL]-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>IM2</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<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=6mkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mkh OCA], [http://pdbe.org/6mkh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mkh RCSB], [http://www.ebi.ac.uk/pdbsum/6mkh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mkh ProSAT]</span></td></tr>
-	[[~~Category~~: D'Andrea, E.D]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Andrea, E D.D]]
		+	[[Category: Moon, T M]]
	[[Category: Page, R]]		[[Category: Page, R]]
	[[Category: Peti, W]]		[[Category: Peti, W]]
-	[[Category: ~~Moon, T.M~~]]	+	[[Category: Antibiotic]]
		+	[[Category: Imipenem]]
		+	[[Category: Inhibitor]]
		+	[[Category: Pbp]]
		+	[[Category: Penicillin-binding protein]]
		+	[[Category: Protein binding-antibiotic complex]]

OCA at 06:29, 10 October 2018

2018-10-10T06:29:29Z

←Older revision		Revision as of 06:29, 10 October 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6mkh is ON HOLD until ~~sometime in the future~~	+	The entry 6mkh is ON HOLD until Paper Publication

	Authors: D'Andrea, E.D., Moon, T.M., Peti, W., Page, R.		Authors: D'Andrea, E.D., Moon, T.M., Peti, W., Page, R.
Line 8:		Line 8:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: D'Andrea, E.D]]		[[Category: D'Andrea, E.D]]
-	[[Category: Peti, W]]
	[[Category: Page, R]]		[[Category: Page, R]]
		+	[[Category: Peti, W]]
	[[Category: Moon, T.M]]		[[Category: Moon, T.M]]

OCA: Protected "6mkh" [edit=sysop:move=sysop]

2018-10-03T06:28:59Z

Protected "6mkh" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:28, 3 October 2018

OCA: New page: '''Unreleased structure''' The entry 6mkh is ON HOLD until sometime in the future Authors: D'Andrea, E.D., Moon, T.M., Peti, W., Page, R. Description: Crystal structure of pencillin bi...

2018-10-03T06:28:57Z

New page: '''Unreleased structure''' The entry 6mkh is ON HOLD until sometime in the future Authors: D'Andrea, E.D., Moon, T.M., Peti, W., Page, R. Description: Crystal structure of pencillin bi...

New page

'''Unreleased structure'''

The entry 6mkh is ON HOLD until sometime in the future

Authors: D'Andrea, E.D., Moon, T.M., Peti, W., Page, R.

Description: Crystal structure of pencillin binding protein 4 (PBP4) from Enterococcus faecalis in the imipenem-bound form
[[Category: Unreleased Structures]]
[[Category: D'Andrea, E.D]]
[[Category: Peti, W]]
[[Category: Page, R]]
[[Category: Moon, T.M]]