7pm4
From Proteopedia
(Difference between revisions)
| Line 4: | Line 4: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7pm4]] 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=7PM4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PM4 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7pm4]] 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=7PM4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PM4 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DFU:(2S,3R,4S,5R)-2-METHYLPIPERIDINE-3,4,5-TRIOL'>DFU</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.49Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DFU:(2S,3R,4S,5R)-2-METHYLPIPERIDINE-3,4,5-TRIOL'>DFU</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7pm4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pm4 OCA], [https://pdbe.org/7pm4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pm4 RCSB], [https://www.ebi.ac.uk/pdbsum/7pm4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pm4 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=7pm4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pm4 OCA], [https://pdbe.org/7pm4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pm4 RCSB], [https://www.ebi.ac.uk/pdbsum/7pm4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pm4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| Line 15: | Line 16: | ||
Enzymatic hydrolysis of alpha-L-fucose from fucosylated glycoconjugates is consequential in bacterial infections and the neurodegenerative lysosomal storage disorder fucosidosis. Understanding human alpha-L-fucosidase catalysis, in an effort toward drug design, has been hindered by the absence of three-dimensional structural data for any animal fucosidase. Here, we have used cryoelectron microscopy (cryo-EM) to determine the structure of human lysosomal alpha-L-fucosidase (FucA1) in both an unliganded state and in complex with the inhibitor deoxyfuconojirimycin. These structures, determined at 2.49 A resolution, reveal the homotetrameric structure of FucA1, the architecture of the catalytic center, and the location of both natural population variations and disease-causing mutations. Furthermore, this work has conclusively identified the hitherto contentious identity of the catalytic acid/base as aspartate-276, representing a shift from both the canonical glutamate acid/base residue and a previously proposed glutamate residue. These findings have furthered our understanding of how FucA1 functions in both health and disease. | Enzymatic hydrolysis of alpha-L-fucose from fucosylated glycoconjugates is consequential in bacterial infections and the neurodegenerative lysosomal storage disorder fucosidosis. Understanding human alpha-L-fucosidase catalysis, in an effort toward drug design, has been hindered by the absence of three-dimensional structural data for any animal fucosidase. Here, we have used cryoelectron microscopy (cryo-EM) to determine the structure of human lysosomal alpha-L-fucosidase (FucA1) in both an unliganded state and in complex with the inhibitor deoxyfuconojirimycin. These structures, determined at 2.49 A resolution, reveal the homotetrameric structure of FucA1, the architecture of the catalytic center, and the location of both natural population variations and disease-causing mutations. Furthermore, this work has conclusively identified the hitherto contentious identity of the catalytic acid/base as aspartate-276, representing a shift from both the canonical glutamate acid/base residue and a previously proposed glutamate residue. These findings have furthered our understanding of how FucA1 functions in both health and disease. | ||
| - | Cryo-EM structures of human fucosidase FucA1 reveal insight into substrate recognition and catalysis.,Armstrong Z, Meek RW, Wu L, Blaza JN, Davies GJ Structure. 2022 | + | Cryo-EM structures of human fucosidase FucA1 reveal insight into substrate recognition and catalysis.,Armstrong Z, Meek RW, Wu L, Blaza JN, Davies GJ Structure. 2022 Oct 6;30(10):1443-1451.e5. doi: 10.1016/j.str.2022.07.001. Epub , 2022 Jul 29. PMID:35907402<ref>PMID:35907402</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
Cryo-EM structures of human fucosidase FucA1 reveal insight into substate recognition and catalysis.
| |||||||||||
Categories: Homo sapiens | Large Structures | Armstrong Z | Blaza JN | Davies GJ | Meek RW | Wu L
