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==crystal structure of Human Methionine aminopeptidase (HsMetAP1b) in complex with KV-P2-4H-05== | ==crystal structure of Human Methionine aminopeptidase (HsMetAP1b) in complex with KV-P2-4H-05== | ||
<StructureSection load='6lzc' size='340' side='right'caption='[[6lzc]]' scene=''> | <StructureSection load='6lzc' size='340' side='right'caption='[[6lzc]], [[Resolution|resolution]] 1.35Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LZC FirstGlance]. <br> | <table><tr><td colspan='2'>[[6lzc]] 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=6LZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LZC FirstGlance]. <br> | ||
</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=6lzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lzc OCA], [https://pdbe.org/6lzc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lzc RCSB], [https://www.ebi.ac.uk/pdbsum/6lzc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lzc ProSAT]</span></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]] 1.35Å</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=EYL:~{N}-oxidanyl-1-(phenylmethyl)pyrrolo[2,3-b]pyridine-4-carboxamide'>EYL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=6lzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lzc OCA], [https://pdbe.org/6lzc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lzc RCSB], [https://www.ebi.ac.uk/pdbsum/6lzc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lzc ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== 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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Methionine aminopeptidases (MetAPs) are an important class of enzymes that work co-translationally for the removal of initiator methionine. Chemical inhibition or gene knockdown is lethal to the microbes suggesting that they can be used as antibiotic targets. However, sequence and structural similarity between the microbial and host MetAPs has been a challenge in the identification of selective inhibitors. In this study, we have analyzed several thousands of MetAP sequences and established a pattern of variation in the S1 pocket of the enzyme. Based on this knowledge, we have designed a library of 17 azaindole based hydroxamic acid derivatives which selectively inhibited the MetAP from H. pylori compared to the human counterpart. Structural studies provided the molecular basis for the selectivity. | |||
Selective inhibition of Helicobacter pylori methionine aminopeptidase by azaindole hydroxamic acid derivatives: Design, synthesis, in vitro biochemical and structural studies.,Bala S, Yellamanda KV, Kadari A, Ravinuthala VSU, Kattula B, Singh OV, Gundla R, Addlagatta A Bioorg Chem. 2021 Jul 21;115:105185. doi: 10.1016/j.bioorg.2021.105185. PMID:34329997<ref>PMID:34329997</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6lzc" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Addlagatta A]] | [[Category: Addlagatta A]] | ||
[[Category: Sandeep CB]] | [[Category: Sandeep CB]] | ||
Latest revision as of 18:06, 29 November 2023
crystal structure of Human Methionine aminopeptidase (HsMetAP1b) in complex with KV-P2-4H-05crystal structure of Human Methionine aminopeptidase (HsMetAP1b) in complex with KV-P2-4H-05
Structural highlights
FunctionMAP11_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 PubMedMethionine aminopeptidases (MetAPs) are an important class of enzymes that work co-translationally for the removal of initiator methionine. Chemical inhibition or gene knockdown is lethal to the microbes suggesting that they can be used as antibiotic targets. However, sequence and structural similarity between the microbial and host MetAPs has been a challenge in the identification of selective inhibitors. In this study, we have analyzed several thousands of MetAP sequences and established a pattern of variation in the S1 pocket of the enzyme. Based on this knowledge, we have designed a library of 17 azaindole based hydroxamic acid derivatives which selectively inhibited the MetAP from H. pylori compared to the human counterpart. Structural studies provided the molecular basis for the selectivity. Selective inhibition of Helicobacter pylori methionine aminopeptidase by azaindole hydroxamic acid derivatives: Design, synthesis, in vitro biochemical and structural studies.,Bala S, Yellamanda KV, Kadari A, Ravinuthala VSU, Kattula B, Singh OV, Gundla R, Addlagatta A Bioorg Chem. 2021 Jul 21;115:105185. doi: 10.1016/j.bioorg.2021.105185. PMID:34329997[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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