2adu

From Proteopedia

(Difference between revisions)

Revision as of 07:22, 23 August 2023

Human Methionine Aminopeptidase Complex with 4-Aryl-1,2,3-triazole Inhibitor

Structural highlights

2adu is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Inhibitors of human methionine aminopeptidase type 2 (hMetAP2) are of interest as potential treatments for cancer. A new class of small molecule reversible inhibitors of hMetAP2 was discovered and optimized, the 4-aryl-1,2,3-triazoles. Compound 24, a potent inhibitor of cobalt-activated hMetAP2, also inhibits human and mouse endothelial cell growth. Using a mouse matrigel model, this reversible hMetAP2 inhibitor was also shown to inhibit angiogenesis in vivo.

4-Aryl-1,2,3-triazole: a novel template for a reversible methionine aminopeptidase 2 inhibitor, optimized to inhibit angiogenesis in vivo.,Kallander LS, Lu Q, Chen W, Tomaszek T, Yang G, Tew D, Meek TD, Hofmann GA, Schulz-Pritchard CK, Smith WW, Janson CA, Ryan MD, Zhang GF, Johanson KO, Kirkpatrick RB, Ho TF, Fisher PW, Mattern MR, Johnson RK, Hansbury MJ, Winkler JD, Ward KW, Veber DF, Thompson SK J Med Chem. 2005 Sep 8;48(18):5644-7. PMID:16134930^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kallander LS, Lu Q, Chen W, Tomaszek T, Yang G, Tew D, Meek TD, Hofmann GA, Schulz-Pritchard CK, Smith WW, Janson CA, Ryan MD, Zhang GF, Johanson KO, Kirkpatrick RB, Ho TF, Fisher PW, Mattern MR, Johnson RK, Hansbury MJ, Winkler JD, Ward KW, Veber DF, Thompson SK. 4-Aryl-1,2,3-triazole: a novel template for a reversible methionine aminopeptidase 2 inhibitor, optimized to inhibit angiogenesis in vivo. J Med Chem. 2005 Sep 8;48(18):5644-7. PMID:16134930 doi:10.1021/jm050408c

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2adu"

@@ Line 3: / Line 3: @@
 <StructureSection load='2adu' size='340' side='right'caption='[[2adu]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2adu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ADU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ADU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2adu]] 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=2ADU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ADU FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=R20:4-(3-METHYLPHENYL)-1H-1,2,3-TRIAZOLE'>R20</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]] 1.9&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">METAP2, MNPEP, P67EIF2 ([https://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=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=R20:4-(3-METHYLPHENYL)-1H-1,2,3-TRIAZOLE'>R20</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Methionyl_aminopeptidase Methionyl aminopeptidase], with EC number [https://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=2adu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2adu OCA], [https://pdbe.org/2adu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2adu RCSB], [https://www.ebi.ac.uk/pdbsum/2adu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2adu ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/AMPM2_HUMAN AMPM2_HUMAN]] Removes the N-terminal methionine from nascent proteins. 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.<ref>PMID:2511207</ref> <ref>PMID:20521764</ref> <ref>PMID:14534293</ref> <ref>PMID:17636946</ref>   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.<ref>PMID:2511207</ref> <ref>PMID:20521764</ref> <ref>PMID:14534293</ref> <ref>PMID:17636946</ref>
+[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.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 37: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Methionyl aminopeptidase]]
+[[Category: Chen W]]
-[[Category: Chen, W]]
+[[Category: Fisher PW]]
-[[Category: Fisher, P W]]
+[[Category: Hansbury MJ]]
-[[Category: Hansbury, M J]]
+[[Category: Ho TF]]
-[[Category: Ho, T F]]
+[[Category: Hofmann GA]]
-[[Category: Hofmann, G A]]
+[[Category: Janson CA]]
-[[Category: Janson, C A]]
+[[Category: Johanson KO]]
-[[Category: Johanson, K O]]
+[[Category: Johnson RK]]
-[[Category: Johnson, R K]]
+[[Category: Kallander LS]]
-[[Category: Kallander, L S]]
+[[Category: Kirkpatrick RB]]
-[[Category: Kirkpatrick, R B]]
+[[Category: Lu Q]]
-[[Category: Lu, Q]]
+[[Category: Mattern MR]]
-[[Category: Mattern, M R]]
+[[Category: Meek TD]]
-[[Category: Meek, T D]]
+[[Category: Ryan MD]]
-[[Category: Ryan, M D]]
+[[Category: Schulz-Pritchard CK]]
-[[Category: Schulz-Pritchard, C K]]
+[[Category: Smith WW]]
-[[Category: Smith, W W]]
+[[Category: Tew D]]
-[[Category: Tew, D]]
+[[Category: Thompson SK]]
-[[Category: Thompson, S K]]
+[[Category: Tomaszek T]]
-[[Category: Tomaszek, T]]
+[[Category: Veber DF]]
-[[Category: Veber, D F]]
+[[Category: Ward KW]]
-[[Category: Ward, K W]]
+[[Category: Winkler JD]]
-[[Category: Winkler, J D]]
+[[Category: Yang G]]
-[[Category: Yang, G]]
+[[Category: Zhang GF]]
-[[Category: Zhang, G F]]
-[[Category: Aminopeptidase]]
-[[Category: Hydrolase]]
-[[Category: Metal binding]]
-[[Category: Protease]]

2adu

From Proteopedia

Revision as of 07:22, 23 August 2023

Human Methionine Aminopeptidase Complex with 4-Aryl-1,2,3-triazole Inhibitor

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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