6q27 - Revision history

OCA at 14:56, 13 March 2024

OCA — Wed, 13 Mar 2024 14:56:03 GMT

←Older revision		Revision as of 14:56, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='6q27' size='340' side='right'caption='[[6q27]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='6q27' size='340' side='right'caption='[[6q27]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6q27]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus~~ aureus~~" (rosenbach 1884) zopf 1885~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q27 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6Q27 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6q27]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q27 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Q27 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=BM3:2-(ACETYLAMINO)~~-2~~-DEOXY-ALPHA-D-MANNOPYRANOSE'>BM3</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]] 2.2Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>bglK, EP54_02970, EQ90_08795, NCTC10654_00349, NCTC10702_00557, RK64_02145 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~1280~~ "~~Micrococcus aureus~~" (~~Rosenbach 1884) Zopf 1885]~~)</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BM3:2-(ACETYLAMINO)-2-DEOXY-ALPHA-D-MANNOPYRANOSE'>BM3</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=6q27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q27 OCA], [~~http~~://pdbe.org/6q27 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6q27 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6q27 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6q27 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=6q27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q27 OCA], [https://pdbe.org/6q27 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6q27 RCSB], [https://www.ebi.ac.uk/pdbsum/6q27 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6q27 ProSAT]</span></td></tr>
	</table>		</table>
-	~~<div style~~=~~"background-color:#fffaf0;">~~	+	== Function ==
-	=~~= Publication Abstract from PubMed~~ ==	+	[https://www.uniprot.org/uniprot/Q2G159_STAA8 Q2G159_STAA8]
-	In environments where glucose is limited, some pathogenic bacteria metabolise host derived sialic acid as a nutrient source. N-Acetylmannosamine kinase (NanK) is the second enzyme of the bacterial sialic acid import and degradation pathway and adds phosphate to N-acetylmannosamine using ATP to prime the molecule for future pathway reactions. Sequence alignments reveal that Gram-positive NanK enzymes belong to the Repressor, Open-reading frame, Kinase (ROK) family, but many lack the canonical Zn-binding motif expected for this function, and the sugar-binding ExGH motif is altered to ExGY. As a result, it is unclear how they perform this important reaction. Here, we study the Staphylococcus aureus NanK (SaNanK), which is the first characterisation of a Gram-positive NanK. We report the kinetic activity of SaNanK along with the ligand-free, N-acetylmannosamine-bound and substrate analog N-acetylglucosamine-bound crystal structures (2.33, 2.20 and 2.20 A resolution, respectively). These demonstrate, in combination with small-angle X-ray scattering, that SaNanK is a dimer that adopts a closed conformation upon substrate binding. Analysis of the ExGY motif reveals that the tyrosine binds to the N-acetyl group to select for the 'boat' conformation of N-acetylmannosamine. Moreover, SaNanK has a stacked arginine pair coordinated by negative residues critical for thermal stability and catalysis. These combined elements serve to constrain the active site and orient the substrate in lieu of Zn binding, representing a significant departure from canonical NanK binding. This characterisation provides insight into differences in the ROK family and highlights a novel area for antimicrobial discovery to fight Gram-positive and S. aureus infections.	+
-		+
-	The basis for non-canonical ROK family function in the N-acetylmannosamine kinase from the pathogen Staphylococcus aureus.,Coombes D, Davies JS, Newton-Vesty MC, Horne CR, Setty TG, Subramanian R, Moir JWB, Friemann R, Panjikar S, Griffin MDW, North RA, Dobson RCJ J Biol Chem. 2020 Jan 15. pii: ~~RA119.010526. doi: 10.1074~~/~~jbc.RA119.010526. PMID:31949045<ref>PMID:31949045<~~/~~ref>~~	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U~~.S. ~~National Library of Medicine.<br>~~	+
-	</~~div>~~	+
-	~~<div class="pdbe-citations 6q27" style="background-color:#fffaf0;"></div>~~	+
-	~~== References ==~~	+
-	~~<references~~/>	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Coombes, D~~]]	+	[[Category: Staphylococcus aureus]]
-	[[Category: ~~Davies, J S~~]]	+	[[Category: Coombes D]]
-	[[Category: ~~Dobson, R C.J~~]]	+	[[Category: Davies JS]]
-	[[Category: ~~Horne, C R~~]]	+	[[Category: Dobson RCJ]]
-	[[Category: ~~Rok]]~~	+	[[Category: Horne CR]]
-	~~[[Category: Sugar kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 16:16, 29 January 2020

OCA — Wed, 29 Jan 2020 16:16:23 GMT

←Older revision		Revision as of 16:16, 29 January 2020
Line 3:		Line 3:
	<StructureSection load='6q27' size='340' side='right'caption='[[6q27]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='6q27' size='340' side='right'caption='[[6q27]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6q27]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q27 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6q27]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q27 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BM3:2-(ACETYLAMINO)-2-DEOXY-ALPHA-D-MANNOPYRANOSE'>BM3</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BM3:2-(ACETYLAMINO)-2-DEOXY-ALPHA-D-MANNOPYRANOSE'>BM3</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">bglK, EP54_02970, EQ90_08795, NCTC10654_00349, NCTC10702_00557, RK64_02145 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</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=6q27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q27 OCA], [http://pdbe.org/6q27 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q27 RCSB], [http://www.ebi.ac.uk/pdbsum/6q27 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q27 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=6q27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q27 OCA], [http://pdbe.org/6q27 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q27 RCSB], [http://www.ebi.ac.uk/pdbsum/6q27 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q27 ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	In environments where glucose is limited, some pathogenic bacteria metabolise host derived sialic acid as a nutrient source. N-Acetylmannosamine kinase (NanK) is the second enzyme of the bacterial sialic acid import and degradation pathway and adds phosphate to N-acetylmannosamine using ATP to prime the molecule for future pathway reactions. Sequence alignments reveal that Gram-positive NanK enzymes belong to the Repressor, Open-reading frame, Kinase (ROK) family, but many lack the canonical Zn-binding motif expected for this function, and the sugar-binding ExGH motif is altered to ExGY. As a result, it is unclear how they perform this important reaction. Here, we study the Staphylococcus aureus NanK (SaNanK), which is the first characterisation of a Gram-positive NanK. We report the kinetic activity of SaNanK along with the ligand-free, N-acetylmannosamine-bound and substrate analog N-acetylglucosamine-bound crystal structures (2.33, 2.20 and 2.20 A resolution, respectively). These demonstrate, in combination with small-angle X-ray scattering, that SaNanK is a dimer that adopts a closed conformation upon substrate binding. Analysis of the ExGY motif reveals that the tyrosine binds to the N-acetyl group to select for the 'boat' conformation of N-acetylmannosamine. Moreover, SaNanK has a stacked arginine pair coordinated by negative residues critical for thermal stability and catalysis. These combined elements serve to constrain the active site and orient the substrate in lieu of Zn binding, representing a significant departure from canonical NanK binding. This characterisation provides insight into differences in the ROK family and highlights a novel area for antimicrobial discovery to fight Gram-positive and S. aureus infections.
		+
		+	The basis for non-canonical ROK family function in the N-acetylmannosamine kinase from the pathogen Staphylococcus aureus.,Coombes D, Davies JS, Newton-Vesty MC, Horne CR, Setty TG, Subramanian R, Moir JWB, Friemann R, Panjikar S, Griffin MDW, North RA, Dobson RCJ J Biol Chem. 2020 Jan 15. pii: RA119.010526. doi: 10.1074/jbc.RA119.010526. PMID:31949045<ref>PMID:31949045</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6q27" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 16:15, 22 January 2020

OCA — Wed, 22 Jan 2020 16:15:30 GMT

←Older revision		Revision as of 16:15, 22 January 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6q27 ~~is ON HOLD until Aug 07 2021~~	+	==N-acetylmannosamine kinase with N-acetylmannosamine from Staphylococcus aureus==
-		+	<StructureSection load='6q27' size='340' side='right'caption='[[6q27]], [[Resolution\|resolution]] 2.20Å' scene=''>
-	~~Authors~~: ~~Coombes, D~~.~~, Horne, C~~.R.~~, Davies, J~~.S.~~, Dobson, R~~.C.J.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6q27]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q27 FirstGlance]. <br>
-	~~Description~~: N-~~acetylmannosamine kinase with N~~-~~acetylmannosamine from Staphylococcus aureus~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BM3:2-(ACETYLAMINO)-2-DEOXY-ALPHA-D-MANNOPYRANOSE'>BM3</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=6q27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q27 OCA], [http://pdbe.org/6q27 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q27 RCSB], [http://www.ebi.ac.uk/pdbsum/6q27 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q27 ProSAT]</span></td></tr>
-	[~~[Category~~: ~~Davies~~, J.S]]	+	</table>
-	[[Category: ~~Horne, C.R~~]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Coombes, D]]		[[Category: Coombes, D]]
-	[[Category: Dobson, R.C.J]]	+	[[Category: Davies, J S]]
		+	[[Category: Dobson, R C.J]]
		+	[[Category: Horne, C R]]
		+	[[Category: Rok]]
		+	[[Category: Sugar kinase]]
		+	[[Category: Transferase]]

OCA at 07:18, 2 October 2019

OCA — Wed, 02 Oct 2019 07:18:30 GMT

←Older revision		Revision as of 07:18, 2 October 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6q27 is ON HOLD	+	The entry 6q27 is ON HOLD until Aug 07 2021

	Authors: Coombes, D., Horne, C.R., Davies, J.S., Dobson, R.C.J.		Authors: Coombes, D., Horne, C.R., Davies, J.S., Dobson, R.C.J.
Line 8:		Line 8:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Davies, J.S]]		[[Category: Davies, J.S]]
-	[[Category: Coombes, D]]
	[[Category: Horne, C.R]]		[[Category: Horne, C.R]]
		+	[[Category: Coombes, D]]
	[[Category: Dobson, R.C.J]]		[[Category: Dobson, R.C.J]]

OCA: Protected "6q27" [edit=sysop:move=sysop]

OCA — Wed, 14 Aug 2019 15:06:40 GMT

Protected "6q27" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:06, 14 August 2019

OCA: New page: '''Unreleased structure''' The entry 6q27 is ON HOLD Authors: Coombes, D., Horne, C.R., Davies, J.S., Dobson, R.C.J. Description: N-acetylmannosamine kinase with N-acetylmannosamine fr...

OCA — Wed, 14 Aug 2019 15:06:38 GMT

New page: '''Unreleased structure''' The entry 6q27 is ON HOLD Authors: Coombes, D., Horne, C.R., Davies, J.S., Dobson, R.C.J. Description: N-acetylmannosamine kinase with N-acetylmannosamine fr...

New page

'''Unreleased structure'''

The entry 6q27 is ON HOLD

Authors: Coombes, D., Horne, C.R., Davies, J.S., Dobson, R.C.J.

Description: N-acetylmannosamine kinase with N-acetylmannosamine from Staphylococcus aureus
[[Category: Unreleased Structures]]
[[Category: Davies, J.S]]
[[Category: Coombes, D]]
[[Category: Horne, C.R]]
[[Category: Dobson, R.C.J]]