7a12 - Revision history

OCA at 12:01, 1 February 2024

OCA — Thu, 01 Feb 2024 12:01:49 GMT

←Older revision		Revision as of 12:01, 1 February 2024
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	<StructureSection load='7a12' size='340' side='right'caption='[[7a12]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='7a12' size='340' side='right'caption='[[7a12]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7a12]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A12 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7A12 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7a12]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A12 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A12 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=QVK:5-chloranyl-3-phenyl-1~{H}-indole-2-carboxamide'>QVK</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]] 2Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">METAP2, MNPEP, P67EIF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=QVK:5-chloranyl-3-phenyl-1~{H}-indole-2-carboxamide'>QVK</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionyl_aminopeptidase Methionyl aminopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.18 3.4.11.18] </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=7a12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a12 OCA], [https://pdbe.org/7a12 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a12 RCSB], [https://www.ebi.ac.uk/pdbsum/7a12 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a12 ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=7a12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a12 OCA], [~~http~~://pdbe.org/7a12 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7a12 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7a12 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7a12 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MAP2_HUMAN MAP2_HUMAN]] Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). The catalytic activity of human METAP2 toward Met-Val peptides is consistently two orders of magnitude higher than that of METAP1, suggesting that it is responsible for processing proteins containing N-terminal Met-Val and Met-Thr sequences in vivo. Protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation by inhibitory kinases such as EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of protein synthesis.	+	[https://www.uniprot.org/uniprot/MAP2_HUMAN MAP2_HUMAN] Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). The catalytic activity of human METAP2 toward Met-Val peptides is consistently two orders of magnitude higher than that of METAP1, suggesting that it is responsible for processing proteins containing N-terminal Met-Val and Met-Thr sequences in vivo. Protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation by inhibitory kinases such as EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of protein synthesis.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7a12" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7a12" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Aminopeptidase 3D structures\|Aminopeptidase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Methionyl aminopeptidase]]~~	+	[[Category: Thorpe JH]]
-	[[Category: Thorpe~~, J H]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Methionine aminopeptidase-2~~]]	+

OCA at 06:20, 14 October 2020

OCA — Wed, 14 Oct 2020 06:20:24 GMT

←Older revision		Revision as of 06:20, 14 October 2020
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	==CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX WITH AN INHIBITOR GW557358X (COMPOUND 9)==		==CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX WITH AN INHIBITOR GW557358X (COMPOUND 9)==
-	<StructureSection load='7a12' size='340' side='right'caption='[[7a12]]' scene=''>	+	<StructureSection load='7a12' size='340' side='right'caption='[[7a12]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A12 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7A12 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7a12]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A12 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7A12 FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7a12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a12 OCA], [http://pdbe.org/7a12 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7a12 RCSB], [http://www.ebi.ac.uk/pdbsum/7a12 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7a12 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=QVK:5-chloranyl-3-phenyl-1~{H}-indole-2-carboxamide'>QVK</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">METAP2, MNPEP, P67EIF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionyl_aminopeptidase Methionyl aminopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.18 3.4.11.18] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7a12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a12 OCA], [http://pdbe.org/7a12 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7a12 RCSB], [http://www.ebi.ac.uk/pdbsum/7a12 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7a12 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MAP2_HUMAN MAP2_HUMAN]] Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). The catalytic activity of human METAP2 toward Met-Val peptides is consistently two orders of magnitude higher than that of METAP1, suggesting that it is responsible for processing proteins containing N-terminal Met-Val and Met-Thr sequences in vivo. Protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation by inhibitory kinases such as EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of protein synthesis.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Structure-based led optimisation of orally active reversible Methionine Aminopeptidase-2 (MetAP-2) inhibitors utilising a 'molecular budget' medicinal chemistry strategy is described. The key physicochemical parameters of target molecules (cLogP, molecular size and H-bond donor count) were monitored through straightforward and intuitive use of atom count and distribution. The balance between structure-based design and an awareness of the physico-chemical properties of the compounds synthesised enabled the rapid identification of a potent molecule with good oral pharmacokinetic (PK) characteristics by making fewer, higher quality compounds. The resulting candidate quality molecule was validated in a mechanistic cellular assay and a rodent secondary immunisation model.
		+
		+	Structure-based optimisation of orally active & reversible MetAP-2 inhibitors maintaining a tight 'molecular budget'.,Hirst DJ, Brandt M, Bruton G, Christodoulou E, Cutler L, Deeks N, Goodacre JD, Jack T, Lindon M, Miah A, Page K, Parr N, Shukla L, Sims M, Thomas P, Thorpe J, Holmes DS Bioorg Med Chem Lett. 2020 Sep 9:127533. doi: 10.1016/j.bmcl.2020.127533. PMID:32919012<ref>PMID:32919012</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7a12" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Thorpe JH]]	+	[[Category: Methionyl aminopeptidase]]
		+	[[Category: Thorpe, J H]]
		+	[[Category: Hydrolase]]
		+	[[Category: Methionine aminopeptidase-2]]

OCA at 11:15, 23 September 2020

OCA — Wed, 23 Sep 2020 11:15:19 GMT

←Older revision		Revision as of 11:15, 23 September 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 7a12 ~~is ON HOLD until Paper Publication~~	+	==CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX WITH AN INHIBITOR GW557358X (COMPOUND 9)==
-		+	<StructureSection load='7a12' size='340' side='right'caption='[[7a12]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A12 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7A12 FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7a12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a12 OCA], [http://pdbe.org/7a12 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7a12 RCSB], [http://www.ebi.ac.uk/pdbsum/7a12 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7a12 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Thorpe JH]]

OCA at 05:01, 2 September 2020

OCA — Wed, 02 Sep 2020 05:01:18 GMT

←Older revision		Revision as of 05:01, 2 September 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7a12 is ON HOLD	+	The entry 7a12 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7a12" [edit=sysop:move=sysop]

OCA — Wed, 19 Aug 2020 04:38:09 GMT

Protected "7a12" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:38, 19 August 2020

OCA: New page: '''Unreleased structure''' The entry 7a12 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 19 Aug 2020 04:38:08 GMT

New page: '''Unreleased structure''' The entry 7a12 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7a12 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]