2gz5: Difference between revisions
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==Human Type 1 methionine aminopeptidase in complex with ovalicin at 1.1 Ang== | ==Human Type 1 methionine aminopeptidase in complex with ovalicin at 1.1 Ang== | ||
<StructureSection load='2gz5' size='340' side='right' caption='[[2gz5]], [[Resolution|resolution]] 1.10Å' scene=''> | <StructureSection load='2gz5' size='340' side='right'caption='[[2gz5]], [[Resolution|resolution]] 1.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2gz5]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2gz5]] 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=2GZ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GZ5 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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=OVA:3,4-DIHYDROXY-2-METHOXY-4-METHYL-3-[2-METHYL-3-(3-METHYL-BUT-2-ENYL)+-OXIRANYL]-CYCLOHEXANONE'>OVA</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=OVA:3,4-DIHYDROXY-2-METHOXY-4-METHYL-3-[2-METHYL-3-(3-METHYL-BUT-2-ENYL)+-OXIRANYL]-CYCLOHEXANONE'>OVA</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2b3k|2b3k]], [[1b59|1b59]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2b3k|2b3k]], [[1b59|1b59]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">METAP1, KIAA0094 ([ | <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'>[ | <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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2gz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gz5 OCA], [https://pdbe.org/2gz5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gz5 RCSB], [https://www.ebi.ac.uk/pdbsum/2gz5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gz5 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> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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==See Also== | ==See Also== | ||
*[[Aminopeptidase|Aminopeptidase]] | *[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Methionyl aminopeptidase]] | [[Category: Methionyl aminopeptidase]] | ||
[[Category: Addlagatta, A]] | [[Category: Addlagatta, A]] | ||
Revision as of 10:27, 17 March 2021
Human Type 1 methionine aminopeptidase in complex with ovalicin at 1.1 AngHuman Type 1 methionine aminopeptidase in complex with ovalicin at 1.1 Ang
Structural highlights
Function[AMPM1_HUMAN] Removes the N-terminal methionine from nascent proteins. Required for normal progression through the cell cycle.[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 PubMedMethionine aminopeptidases (MetAPs) remove the initiator methionine during protein biosynthesis. They exist in two isoforms, MetAP1 and MetAP2. The anti-angiogenic compound fumagillin binds tightly to the Type 2 MetAPs but only weakly to Type 1. High-affinity complexes of fumagillin and its relative ovalicin with Type 2 human MetAP have been reported. Here we describe the crystallographic structure of the low-affinity complex between ovalicin and Type 1 human MetAP at 1.1 A resolution. This provides the first opportunity to compare the structures of ovalicin or fumagillin bound to a Type 1 and a Type 2 MetAP. For both Type 1 and Type 2 human MetAPs the inhibitor makes a covalent adduct with a corresponding histidine. At the same time there are significant differences in the alignment of the inhibitors within the respective active sites. It has been argued that the lower affinity of ovalicin and fumagillin for the Type 1 MetAPs is due to the smaller size of their active sites relative to the Type 2 enzymes. Comparison with the uncomplexed structure of human Type 1 MetAP indicates that there is some truth to this. Several active site residues have to move "outward" by 0.5 Angstroms or so to accommodate the inhibitor. Other residues move "inward." There are, however, other factors that come into play. In particular, the side chain of His310 rotates by 134 degrees into a different position where (together with Glu128 and Tyr195) it coordinates a metal ion not seen at this site in the native enzyme. Structure of the angiogenesis inhibitor ovalicin bound to its noncognate target, human Type 1 methionine aminopeptidase.,Addlagatta A, Matthews BW Protein Sci. 2006 Aug;15(8):1842-8. Epub 2006 Jul 5. PMID:16823043[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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