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| | <StructureSection load='6lzb' size='340' side='right'caption='[[6lzb]], [[Resolution|resolution]] 1.29Å' scene=''> | | <StructureSection load='6lzb' size='340' side='right'caption='[[6lzb]], [[Resolution|resolution]] 1.29Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6lzb]] 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=6LZB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LZB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6lzb]] 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=6LZB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LZB 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=EYF:1-[(3-methoxyphenyl)methyl]-~{N}-oxidanyl-pyrrolo[2,3-b]pyridine-5-carboxamide'>EYF</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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.29Å</td></tr> |
| - | <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='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=EYF:1-[(3-methoxyphenyl)methyl]-~{N}-oxidanyl-pyrrolo[2,3-b]pyridine-5-carboxamide'>EYF</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='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'>[https://proteopedia.org/fgij/fg.htm?mol=6lzb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lzb OCA], [https://pdbe.org/6lzb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lzb RCSB], [https://www.ebi.ac.uk/pdbsum/6lzb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lzb 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=6lzb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lzb OCA], [https://pdbe.org/6lzb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lzb RCSB], [https://www.ebi.ac.uk/pdbsum/6lzb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lzb 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Methionyl aminopeptidase]]
| + | [[Category: Addlagatta A]] |
| - | [[Category: Addlagatta, A]] | + | [[Category: Sandeep CB]] |
| - | [[Category: Sandeep, C B]] | + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Methionine aminopeptidase]]
| + | |
| Structural highlights
6lzb is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.29Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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) 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 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
- ↑ Bala S, Yellamanda KV, Kadari A, Ravinuthala VSU, Kattula B, Singh OV, Gundla R, Addlagatta A. Selective inhibition of Helicobacter pylori methionine aminopeptidase by azaindole hydroxamic acid derivatives: Design, synthesis, in vitro biochemical and structural studies. Bioorg Chem. 2021 Jul 21;115:105185. doi: 10.1016/j.bioorg.2021.105185. PMID:34329997 doi:http://dx.doi.org/10.1016/j.bioorg.2021.105185
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