6ea2 - Revision history

OCA at 14:40, 13 March 2024

2024-03-13T14:40:22Z

← Older revision		Revision as of 14:40, 13 March 2024
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	<StructureSection load='6ea2' size='340' side='right'caption='[[6ea2]], [[Resolution\|resolution]] 1.35Å' scene=''>		<StructureSection load='6ea2' size='340' side='right'caption='[[6ea2]], [[Resolution\|resolution]] 1.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6ea2]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Plafq Plafq~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EA2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6EA2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[6ea2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_FcB1/Columbia Plasmodium falciparum FcB1/Columbia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EA2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=J1G:N-[(1R)-2-(hydroxyamino)-2-oxo-1-(3,4,5-trifluoro[1,1-biphenyl]-4-yl)ethyl]cyclopentanecarboxamide'>J1G</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.35Å</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=6ea2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ea2 OCA], [~~http~~://pdbe.org/6ea2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ea2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ea2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ea2 ProSAT]</span></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=J1G:N-[(1R)-2-(hydroxyamino)-2-oxo-1-(3,4,5-trifluoro[1,1-biphenyl]-4-yl)ethyl]cyclopentanecarboxamide'>J1G</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6ea2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ea2 OCA], [https://pdbe.org/6ea2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ea2 RCSB], [https://www.ebi.ac.uk/pdbsum/6ea2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ea2 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/AMP1_PLAFQ AMP1_PLAFQ]] Displays aminopeptidase activity with a broad substrate specificity. Preferentially hydrolyzes L-Lys-AMC but also shows strong activity against L-Ala-AMC, L-Arg-AMC and L-Leu-AMC.<ref>PMID:12166515</ref> <ref>PMID:19196988</ref>		[https://www.uniprot.org/uniprot/AMP1_PLAFQ AMP1_PLAFQ] Displays aminopeptidase activity with a broad substrate specificity. Preferentially hydrolyzes L-Lys-AMC but also shows strong activity against L-Ala-AMC, L-Arg-AMC and L-Leu-AMC.<ref>PMID:12166515</ref> <ref>PMID:19196988</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	There is an urgent clinical need for antimalarial compounds that target malaria caused by both Plasmodium falciparum and Plasmodium vivax. The M1 and M17 metalloexopeptidases play key roles in Plasmodium haemoglobin digestion, and are validated drug targets. We used a multi-target strategy to rationally design inhibitors capable of potent inhibition of the M1 and M17 aminopeptidases from both P. falciparum (Pf-M1 and Pf-M17) and P. vivax (Pv-M1 and Pv-M17). The novel chemical series contains a hydroxamic acid zinc binding group to coordinate catalytic zinc ion/s, and a variety of hydrophobic groups to probe the S1' pockets of the four target enzymes. Structural characterisation by co-crystallisation showed that selected compounds utilise new and unexpected binding modes; most notably, compounds substituted with bulky hydrophobic substituents displace the Pf-M17 catalytic zinc ion. Excitingly, key compounds of the series potently inhibit all four molecular targets and show antimalarial activity comparable to current clinical candidates.

	Hydroxamic acid inhibitors provide cross-species inhibition of Plasmodium M1 and M17 aminopeptidases.,Vinh NB, Drinkwater N, Malcolm TR, Kassiou M, Lucantoni L, Grin PM, Butler GS, Duffy S, Overall CM, Avery VM, Scammells PJ, McGowan S J Med Chem. 2018 Dec 11. doi: 10.1021/acs.jmedchem.8b01310. PMID:30537832<ref>PMID:30537832</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 6ea2" style="background-color:#fffaf0;"></div~~>

	==See Also==		==See Also==
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: ~~Plafq~~]]		[[Category: Plasmodium falciparum FcB1/Columbia]]
	[[Category: Drinkwater, N]]		[[Category: Drinkwater N]]
	[[Category: McGowan, S]]		[[Category: McGowan S]]
	~~[[Category: Hydrolase]]~~
	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~
	~~[[Category: Hydroxamic acid]]~~
	~~[[Category: Inhibitor]]~~
	~~[[Category: M1 alanyl-aminopeptidase]]~~
	~~[[Category: Protease~~]]

OCA at 07:49, 24 April 2019

2019-04-24T07:49:54Z

← Older revision		Revision as of 07:49, 24 April 2019
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	==X-ray crystal structure of Pf-M1 in complex with inhibitor (6h) and catalytic zinc ion==		==X-ray crystal structure of Pf-M1 in complex with inhibitor (6h) and catalytic zinc ion==
	<StructureSection load='6ea2' size='340' side='right' caption='[[6ea2]], [[Resolution\|resolution]] 1.35Å' scene=''>		<StructureSection load='6ea2' size='340' side='right'caption='[[6ea2]], [[Resolution\|resolution]] 1.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6ea2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EA2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EA2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[6ea2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Plafq Plafq]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EA2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EA2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=J1G:N-[(1R)-2-(hydroxyamino)-2-oxo-1-(3,4,5-trifluoro[1,1-biphenyl]-4-yl)ethyl]cyclopentanecarboxamide'>J1G</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=J1G:N-[(1R)-2-(hydroxyamino)-2-oxo-1-(3,4,5-trifluoro[1,1-biphenyl]-4-yl)ethyl]cyclopentanecarboxamide'>J1G</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6ea2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ea2 OCA], [http://pdbe.org/6ea2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ea2 RCSB], [http://www.ebi.ac.uk/pdbsum/6ea2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ea2 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=6ea2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ea2 OCA], [http://pdbe.org/6ea2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ea2 RCSB], [http://www.ebi.ac.uk/pdbsum/6ea2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ea2 ProSAT]</span></td></tr>
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	</div>		</div>
	<div class="pdbe-citations 6ea2" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6ea2" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Aminopeptidase 3D structures\|Aminopeptidase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Large Structures]]
			[[Category: Plafq]]
	[[Category: Drinkwater, N]]		[[Category: Drinkwater, N]]
	[[Category: McGowan, S]]		[[Category: McGowan, S]]

OCA at 08:17, 26 December 2018

2018-12-26T08:17:54Z

@@ Line 1: / Line 1: @@
-The entry 6ea2 is ON HOLD  until Aug 02 2020
+==X-ray crystal structure of Pf-M1 in complex with inhibitor (6h) and catalytic zinc ion==
-Authors: Drinkwater, N., McGowan, S.
+Hydroxamic acid inhibitors provide cross-species inhibition of Plasmodium M1 and M17 aminopeptidases.,Vinh NB, Drinkwater N, Malcolm TR, Kassiou M, Lucantoni L, Grin PM, Butler GS, Duffy S, Overall CM, Avery VM, Scammells PJ, McGowan S J Med Chem. 2018 Dec 11. doi: 10.1021/acs.jmedchem.8b01310. PMID:30537832<ref>PMID:30537832</ref>
-Description: X-ray crystal structure of Pf-M1 in complex with inhibitor (6h) and catalytic zinc ion
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
 [[Category: Drinkwater, N]]
-[[Category: Mcgowan, S]]
+[[Category: McGowan, S]]

OCA at 04:41, 22 August 2018

2018-08-22T04:41:27Z

← Older revision		Revision as of 04:41, 22 August 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 6ea2 is ON HOLD		The entry 6ea2 is ON HOLD until Aug 02 2020

	Authors: Drinkwater, N., McGowan, S.		Authors: Drinkwater, N., McGowan, S.

OCA: Protected "6ea2" [edit=sysop:move=sysop]

2018-08-09T19:58:12Z

Protected "6ea2" [edit=sysop:move=sysop]

← Older revision	Revision as of 19:58, 9 August 2018
(No difference)

OCA: New page: '''Unreleased structure''' The entry 6ea2 is ON HOLD Authors: Drinkwater, N., McGowan, S. Description: X-ray crystal structure of Pf-M1 in complex with inhibitor (6h) and catalytic zin...

2018-08-09T19:58:11Z

New page: '''Unreleased structure''' The entry 6ea2 is ON HOLD Authors: Drinkwater, N., McGowan, S. Description: X-ray crystal structure of Pf-M1 in complex with inhibitor (6h) and catalytic zin...

New page

'''Unreleased structure'''

The entry 6ea2 is ON HOLD

Authors: Drinkwater, N., McGowan, S.

Description: X-ray crystal structure of Pf-M1 in complex with inhibitor (6h) and catalytic zinc ion
[[Category: Unreleased Structures]]
[[Category: Drinkwater, N]]
[[Category: Mcgowan, S]]