4iu6: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Human Methionine Aminopeptidase in complex with FZ1: Pyridinylquinazolines Selectively Inhibit Human Methionine Aminopeptidase-1== | |||
<StructureSection load='4iu6' size='340' side='right' caption='[[4iu6]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== 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> | |||
</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> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hxx|4hxx]], [[2g6p|2g6p]]</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://www.rcsb.org/pdb/explore.do?structureId=4iu6 RCSB], [http://www.ebi.ac.uk/pdbsum/4iu6 PDBsum]</span></td></tr> | |||
</table> | |||
<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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Aminopeptidase|Aminopeptidase]] | *[[Aminopeptidase|Aminopeptidase]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Methionyl aminopeptidase]] | [[Category: Methionyl aminopeptidase]] | ||
[[Category: Amzel, L M | [[Category: Amzel, L M]] | ||
[[Category: Gabelli, S B | [[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: Hydrolase-hydrolase inhibitor complex]] | ||
[[Category: Metap1]] | [[Category: Metap1]] | ||
[[Category: Methionine aminopeptidase]] | [[Category: Methionine aminopeptidase]] | ||
[[Category: Methionine aminopeptidase 1]] | [[Category: Methionine aminopeptidase 1]] | ||
