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| | <StructureSection load='2nq7' size='340' side='right'caption='[[2nq7]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='2nq7' size='340' side='right'caption='[[2nq7]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2nq7]] 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=2NQ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NQ7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2nq7]] 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=2NQ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NQ7 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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HM5:3-[(2,2-DIMETHYLPROPANOYL)AMINO]-N-1,3-THIAZOL-2-YLPYRIDINE-2-CARBOXAMIDE'>HM5</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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]] 1.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2g6p|2g6p]], [[2nq6|2nq6]]</div></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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HM5:3-[(2,2-DIMETHYLPROPANOYL)AMINO]-N-1,3-THIAZOL-2-YLPYRIDINE-2-CARBOXAMIDE'>HM5</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">METAP1, KIAA0094 ([https://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'>[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=2nq7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nq7 OCA], [https://pdbe.org/2nq7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nq7 RCSB], [https://www.ebi.ac.uk/pdbsum/2nq7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nq7 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=2nq7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nq7 OCA], [https://pdbe.org/2nq7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nq7 RCSB], [https://www.ebi.ac.uk/pdbsum/2nq7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nq7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/AMPM1_HUMAN AMPM1_HUMAN]] Removes the N-terminal methionine from nascent proteins. Required for normal progression through the cell cycle.<ref>PMID:16274222</ref> <ref>PMID:17114291</ref>
| + | [https://www.uniprot.org/uniprot/MAP11_HUMAN MAP11_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). Required for normal progression through the cell cycle.[HAMAP-Rule:MF_03174]<ref>PMID:16274222</ref> <ref>PMID:17114291</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Methionyl aminopeptidase]]
| + | [[Category: Addlagatta A]] |
| - | [[Category: Addlagatta, A]] | + | [[Category: Matthews BW]] |
| - | [[Category: Matthews, B W]] | + | |
| - | [[Category: Cell cycle]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Pita bread]]
| + | |
| - | [[Category: Type 1 human methionine aminopeptidase]]
| + | |
| Structural highlights
Function
MAP11_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). Required for normal progression through the cell cycle.[HAMAP-Rule:MF_03174][1] [2]
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
Processing of the N-terminal initiator methionine is an essential cellular process conserved from prokaryotes to eukaryotes. The enzymes that remove N-terminal methionine are known as methionine aminopeptidases (MetAPs). Human MetAP2 has been shown to be required for the proliferation of endothelial cells and angiogenesis. The physiological function of MetAP1, however, has remained elusive. In this report we demonstrate that a family of inhibitors with a core structure of pyridine-2-carboxylic acid previously developed for the bacterial and yeast MetAP1 is also specific for human MetAP1 (HsMetAP1), as confirmed by both enzymatic assay and high-resolution x-ray crystallography. Treatment of tumor cell lines with the MetAP1-specific inhibitors led to an accumulation of cells in the G(2)/M phase, suggesting that HsMetAP1 may play an important role in G(2)/M phase transition. Overexpression of HsMetAP1, but not HsMetAP2, conferred resistance of cells to the inhibitors, and the inhibitors caused retention of N-terminal methionine of a known MetAP substrate, suggesting that HsMetAP1 is the cellular target for the inhibitors. In addition, when HsMetAP1 was knocked down by gene-specific siRNA, cells exhibited slower progression during G(2)/M phase, a phenotype similar to cells treated with MetAP1 inhibitors. Importantly, MetAP1 inhibitors were able to induce apoptosis of leukemia cell lines, presumably as a consequence of their interference with the G(2)/M phase checkpoint. Together, these results suggest that MetAP1 plays an important role in G(2)/M phase of the cell cycle and that it may serve as a promising target for the discovery and development of new anticancer agents.
Elucidation of the function of type 1 human methionine aminopeptidase during cell cycle progression.,Hu X, Addlagatta A, Lu J, Matthews BW, Liu JO Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18148-53. Epub 2006 Nov 17. PMID:17114291[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Addlagatta A, Hu X, Liu JO, Matthews BW. Structural basis for the functional differences between type I and type II human methionine aminopeptidases. Biochemistry. 2005 Nov 15;44(45):14741-9. PMID:16274222 doi:10.1021/bi051691k
- ↑ Hu X, Addlagatta A, Lu J, Matthews BW, Liu JO. Elucidation of the function of type 1 human methionine aminopeptidase during cell cycle progression. Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18148-53. Epub 2006 Nov 17. PMID:17114291
- ↑ Hu X, Addlagatta A, Lu J, Matthews BW, Liu JO. Elucidation of the function of type 1 human methionine aminopeptidase during cell cycle progression. Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18148-53. Epub 2006 Nov 17. PMID:17114291
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