7kpu
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Crystal structure of human NatD (NAA40) bound to a bisubstrate analogue with a C-3 linker== |
| - | <StructureSection load='7kpu' size='340' side='right'caption='[[7kpu]]' scene=''> | + | <StructureSection load='7kpu' size='340' side='right'caption='[[7kpu]], [[Resolution|resolution]] 1.43Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7kpu]] is a 4 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=7KPU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KPU 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=7kpu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kpu OCA], [https://pdbe.org/7kpu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kpu RCSB], [https://www.ebi.ac.uk/pdbsum/7kpu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kpu 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]] 1.43Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=WZG:[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]methyl+(3R)-3-hydroxy-2,2-dimethyl-4-[(3-{[2-(methylsulfanyl)ethyl]amino}-3-oxopropyl)amino]-4-oxobutyl+dihydrogen+diphosphate+(non-preferred+name)'>WZG</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=7kpu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kpu OCA], [https://pdbe.org/7kpu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kpu RCSB], [https://www.ebi.ac.uk/pdbsum/7kpu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kpu ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/NAA40_HUMAN NAA40_HUMAN] Responsible for the acetylation of the N-terminal residues of histones H4 and H2A.<ref>PMID:21935442</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Protein N-terminal acetyltransferase D (NatD, NAA40) that specifically acetylates the alpha-N-terminus of histone H4 and H2A has been implicated in various diseases, but no inhibitor has been reported for this important enzyme. Based on the acetyl transfer mechanism of NatD, we designed and prepared a series of highly potent NatD bisubstrate inhibitors by covalently linking coenzyme A to different peptide substrates via an acetyl or propionyl spacer. The most potent bisubstrate inhibitor displayed an apparent K(i) value of 1.0 nM. Biochemical studies indicated that bisubstrate inhibitors are competitive to the peptide substrate and noncompetitive to the cofactor, suggesting that NatD undergoes an ordered Bi-Bi mechanism. We also demonstrated that these inhibitors are highly specific toward NatD, displaying about 1000-fold selectivity over other closely related acetyltransferases. High-resolution crystal structures of NatD bound to two of these inhibitors revealed the molecular basis for their selectivity and inhibition mechanism, providing a rational path for future inhibitor development. | ||
| + | |||
| + | Novel Bisubstrate Inhibitors for Protein N-Terminal Acetyltransferase D.,Deng Y, Deng S, Ho YH, Gardner SM, Huang Z, Marmorstein R, Huang R J Med Chem. 2021 Jun 24;64(12):8263-8271. doi: 10.1021/acs.jmedchem.1c00141. Epub , 2021 Jun 10. PMID:34110812<ref>PMID:34110812</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7kpu" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Deng S]] |
| + | [[Category: Marmorstein R]] | ||
Current revision
Crystal structure of human NatD (NAA40) bound to a bisubstrate analogue with a C-3 linker
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