|
|
| Line 3: |
Line 3: |
| | <StructureSection load='4iu6' size='340' side='right'caption='[[4iu6]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='4iu6' size='340' side='right'caption='[[4iu6]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4iu6]] 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=4IU6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IU6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4iu6]] 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=4IU6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IU6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=FZ1:4-[4-(4-METHOXYPHENYL)PIPERAZIN-1-YL]-2-(PYRIDIN-2-YL)QUINAZOLINE'>FZ1</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </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=FZ1:4-[4-(4-METHOXYPHENYL)PIPERAZIN-1-YL]-2-(PYRIDIN-2-YL)QUINAZOLINE'>FZ1</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hxx|4hxx]], [[2g6p|2g6p]]</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=4iu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iu6 OCA], [https://pdbe.org/4iu6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iu6 RCSB], [https://www.ebi.ac.uk/pdbsum/4iu6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iu6 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">METAP1, KIAA0094 ([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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4iu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iu6 OCA], [http://pdbe.org/4iu6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iu6 RCSB], [http://www.ebi.ac.uk/pdbsum/4iu6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iu6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 28: |
Line 25: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Methionyl aminopeptidase]]
| + | [[Category: Amzel LM]] |
| - | [[Category: Amzel, L M]] | + | [[Category: Gabelli SB]] |
| - | [[Category: Gabelli, S B]] | + | [[Category: Liu J]] |
| - | [[Category: Liu, J]] | + | [[Category: Miller M]] |
| - | [[Category: Miller, M]] | + | [[Category: Zhang F]] |
| - | [[Category: Zhang, F]] | + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Metap1]]
| + | |
| - | [[Category: Methionine aminopeptidase]]
| + | |
| - | [[Category: Methionine aminopeptidase 1]]
| + | |
| 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]
Publication Abstract from PubMed
Methionine aminopeptidases (MetAPs), which remove the initiator methionine from nascent peptides, are essential in all organisms. While MetAP2 has been demonstrated to be a therapeutic target for inhibiting angiogenesis in mammals, MetAP1 seems to be vital for cell proliferation. Our earlier efforts identified two structural classes of human MetAP1 (HsMetAP1)-selective inhibitors (1-4), but all of them failed to inhibit cellular HsMetAP1. Using Mn(II) or Zn(II) to activate HsMetAP1, we found that 1-4 could only effectively inhibit purified HsMetAP1 in the presence of physiologically unachievable concentrations of Co(II). In an effort to seek Co(II)-independent inhibitors, a novel structural class containing a 2-(pyridin-2-yl)quinazoline core has been discovered. Many compounds in this class potently and selectively inhibited HsMetAP1 without Co(II). Subsequently, we demonstrated that 11j, an auxiliary metal-dependent inhibitor, effectively inhibited HsMetAP1 in primary cells. This is the first report that an HsMetAP1-selective inhibitor is effective against its target in cells.
Pyridinylquinazolines selectively inhibit human methionine aminopeptidase-1 in cells.,Zhang F, Bhat S, Gabelli SB, Chen X, Miller MS, Nacev BA, Cheng YL, Meyers DJ, Tenney K, Shim JS, Crews P, Amzel LM, Ma D, Liu JO J Med Chem. 2013 May 23;56(10):3996-4016. doi: 10.1021/jm400227z. Epub 2013 May, 1. PMID:23634668[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
- ↑ Zhang F, Bhat S, Gabelli SB, Chen X, Miller MS, Nacev BA, Cheng YL, Meyers DJ, Tenney K, Shim JS, Crews P, Amzel LM, Ma D, Liu JO. Pyridinylquinazolines selectively inhibit human methionine aminopeptidase-1 in cells. J Med Chem. 2013 May 23;56(10):3996-4016. doi: 10.1021/jm400227z. Epub 2013 May, 1. PMID:23634668 doi:http://dx.doi.org/10.1021/jm400227z
|
