6o55 - Revision history

OCA at 19:28, 29 May 2024

OCA — Wed, 29 May 2024 19:28:28 GMT

←Older revision		Revision as of 19:28, 29 May 2024
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/Q5ZYZ3_LEGPH Q5ZYZ3_LEGPH] Catalyzes the conversion of N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) to 4-carboxy-5-aminoimidazole ribonucleotide (CAIR).[HAMAP-Rule:MF_01929][PIRNR:PIRNR001338]		[https://www.uniprot.org/uniprot/Q5ZYZ3_LEGPH Q5ZYZ3_LEGPH] Catalyzes the conversion of N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) to 4-carboxy-5-aminoimidazole ribonucleotide (CAIR).[HAMAP-Rule:MF_01929][PIRNR:PIRNR001338]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Because purine nucleotides are essential for all life, differences between how microbes and humans metabolize purines can be exploited for the development of antimicrobial therapies. While humans biosynthesize purine nucleotides in a 10-step pathway, most microbes utilize an additional 11th enzymatic activity. The human enzyme, aminoimidazole ribonucleotide (AIR) carboxylase generates the product 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) directly. Most microbes, however, require two separate enzymes, a synthetase (PurK) and a mutase (PurE), and proceed through the intermediate, N(5)-CAIR. Toward the development of therapeutics that target these differences, we have solved crystal structures of the N(5)-CAIR mutase of the human pathogens Legionella pneumophila (LpPurE) and Burkholderia cenocepacia (BcPurE) and used a structure-guided approach to identify inhibitors. Analysis of the structures reveals a highly conserved fold and active site architecture. Using this data, and three additional structures of PurE enzymes, we screened a library of FDA-approved compounds in silico and identified a set of 25 candidates for further analysis. Among these, we identified several new PurE inhibitors with micromolar IC(50) values. Several of these compounds, including the alpha(1)-blocker Alfuzosin, inhibit the microbial PurE enzymes much more effectively than the human homologue. These structures and the newly described PurE inhibitors are valuable tools to aid in further studies of this enzyme and provide a foundation for the development of compounds that target differences between human and microbial purine metabolism.
		+
		+	Structure-Guided Discovery of N(5)-CAIR Mutase Inhibitors.,Belfon KKJ, Sharma N, Zigweid R, Bolejack M, Davies D, Edwards TE, Myler PJ, French JB Biochemistry. 2023 Sep 5;62(17):2587-2596. doi: 10.1021/acs.biochem.2c00705. Epub , 2023 Aug 8. PMID:37552766<ref>PMID:37552766</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6o55" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Phosphoribosylaminoimidazole carboxylase 3D structures\|Phosphoribosylaminoimidazole carboxylase 3D structures]]		*[[Phosphoribosylaminoimidazole carboxylase 3D structures\|Phosphoribosylaminoimidazole carboxylase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 07:04, 11 October 2023

OCA — Wed, 11 Oct 2023 07:04:43 GMT

←Older revision		Revision as of 07:04, 11 October 2023
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	<StructureSection load='6o55' size='340' side='right'caption='[[6o55]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='6o55' size='340' side='right'caption='[[6o55]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6o55]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O55 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6O55 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6o55]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Legionella_pneumophila_subsp._pneumophila_str._Philadelphia_1 Legionella pneumophila subsp. pneumophila str. Philadelphia 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O55 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O55 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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]] 1.7Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/5-(carboxyamino)imidazole_ribonucleotide_mutase 5-(carboxyamino)imidazole ribonucleotide mutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.99.18 5.4.99.18] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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=6o55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o55 OCA], [~~http~~://pdbe.org/6o55 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6o55 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6o55 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6o55 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=6o55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o55 OCA], [https://pdbe.org/6o55 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o55 RCSB], [https://www.ebi.ac.uk/pdbsum/6o55 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o55 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/Q5ZYZ3_LEGPH Q5ZYZ3_LEGPH]] Catalyzes the conversion of N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) to 4-carboxy-5-aminoimidazole ribonucleotide (CAIR).[HAMAP-Rule:MF_01929][PIRNR:PIRNR001338]	+	[https://www.uniprot.org/uniprot/Q5ZYZ3_LEGPH Q5ZYZ3_LEGPH] Catalyzes the conversion of N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) to 4-carboxy-5-aminoimidazole ribonucleotide (CAIR).[HAMAP-Rule:MF_01929][PIRNR:PIRNR001338]
		+
		+	==See Also==
		+	*[[Phosphoribosylaminoimidazole carboxylase 3D structures\|Phosphoribosylaminoimidazole carboxylase 3D structures]]
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Legionella pneumophila subsp. pneumophila str. Philadelphia 1]]
	[[Category: Structural genomic]]		[[Category: Structural genomic]]
-	[[Category: Carboxylase]]
-	[[Category: Isomerase]]
-	[[Category: Mutase]]
-	[[Category: Phosphorobosylaminoimidazole carboxylase]]
-	[[Category: Ssgcid]]

OCA: Protected "6o55" [edit=sysop:move=sysop]

OCA — Wed, 13 Mar 2019 12:24:39 GMT

Protected "6o55" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:24, 13 March 2019

OCA: New page: ==Crystal Structure of N5-carboxyaminoimidazole ribonucleotide mutase (PurE) from Legionella pneumophila== == Structural highlights ==
<table><tr><td colspan='2'>[[6o55]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O55 OCA]. For a guided tour on the structure components use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O55 FirstGlance]. 
</td></tr><tr id='ligand'><td class="sblockLbl">[[Ligand|Ligands:]]</td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
<tr id='activity'><td class="sblockLbl">Activity:</td><td class="sblockDat">[http://en.wikipedia.org/wiki/5-(carboxyamino)imidazole_ribonucleotide_mutase 5-(carboxyamino)imidazole ribonucleotide mutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.99.18 5.4.99.18] </td></tr>
<tr id='resources'><td class="sblockLbl">Resources:</td><td class="sblockDat">[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6o55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o55 OCA], [http://pdbe.org/6o55 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o55 RCSB], [http://www.ebi.ac.uk/pdbsum/6o55 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o55 ProSAT]</td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/Q5ZYZ3_LEGPH Q5ZYZ3_LEGPH]] Catalyzes the conversion of N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) to 4-carboxy-5-aminoimidazole ribonucleotide (CAIR).[HAMAP-Rule:MF_01929][PIRNR:PIRNR001338]
TOC
</StructureSection>
[[Category: Large Structures]]
[[Category: Structural genomic]]
[[Category: Carboxylase]]
[[Category: Isomerase]]
[[Category: Mutase]]
[[Category: Phosphorobosylaminoimidazole carboxylase]]
[[Category: Ssgcid]]