4iu6
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<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> | <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" 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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</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='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='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> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[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> | [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;"> | ||
| - | == 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. | ||
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| - | 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<ref>PMID:23634668</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4iu6" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
Human Methionine Aminopeptidase in complex with FZ1: Pyridinylquinazolines Selectively Inhibit Human Methionine Aminopeptidase-1
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Categories: Homo sapiens | Large Structures | Amzel LM | Gabelli SB | Liu J | Miller M | Zhang F
