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| | ==Crystal Structure of Human Asparaginase-like Protein 1 Thr168Ala== | | ==Crystal Structure of Human Asparaginase-like Protein 1 Thr168Ala== |
| - | <StructureSection load='3tkj' size='340' side='right' caption='[[3tkj]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='3tkj' size='340' side='right'caption='[[3tkj]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3tkj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TKJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TKJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3tkj]] is a 2 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=3TKJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TKJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</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]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3tkx|3tkx]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ASRGL1, ALP, CRASH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3tkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tkj OCA], [https://pdbe.org/3tkj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tkj RCSB], [https://www.ebi.ac.uk/pdbsum/3tkj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tkj ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Asparaginase Asparaginase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.1 3.5.1.1] </span></td></tr> | + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tkj OCA], [http://pdbe.org/3tkj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tkj RCSB], [http://www.ebi.ac.uk/pdbsum/3tkj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tkj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ASGL1_HUMAN ASGL1_HUMAN]] Has both L-asparaginase and beta-aspartyl peptidase activity. May be involved in the production of L-aspartate, which can act as an excitatory neurotransmitter in some brain regions. Is highly active with L-Asp beta-methyl ester. Besides, has catalytic activity toward beta-aspartyl dipeptides and their methyl esters, including beta-L-Asp-L-Phe, beta-L-Asp-L-Phe methyl ester (aspartame), beta-L-Asp-L-Ala, beta-L-Asp-L-Leu and beta-L-Asp-L-Lys. Does not have aspartylglucosaminidase activity and is inactive toward GlcNAc-L-Asn. Likewise, has no activity toward glutamine.<ref>PMID:19839645</ref> | + | [https://www.uniprot.org/uniprot/ASGL1_HUMAN ASGL1_HUMAN] Has both L-asparaginase and beta-aspartyl peptidase activity. May be involved in the production of L-aspartate, which can act as an excitatory neurotransmitter in some brain regions. Is highly active with L-Asp beta-methyl ester. Besides, has catalytic activity toward beta-aspartyl dipeptides and their methyl esters, including beta-L-Asp-L-Phe, beta-L-Asp-L-Phe methyl ester (aspartame), beta-L-Asp-L-Ala, beta-L-Asp-L-Leu and beta-L-Asp-L-Lys. Does not have aspartylglucosaminidase activity and is inactive toward GlcNAc-L-Asn. Likewise, has no activity toward glutamine.<ref>PMID:19839645</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The human asparaginase-like protein 1 (hASRGL1) catalyzes the hydrolysis of l-asparagine and isoaspartyl-dipeptides. As an N-terminal nucleophile (Ntn) hydrolase superfamily member, the active form of hASRGL1 is generated by an intramolecular cleavage step with Thr168 as the catalytic residue. However, in vitro, autoprocessing is incomplete ( approximately 50%), fettering the biophysical characterization of hASRGL1. We circumvented this obstacle by constructing a circularly permuted hASRGL1 that uncoupled the autoprocessing reaction, allowing us to kinetically and structurally characterize this enzyme and the precursor-like hASRGL1-Thr168Ala variant. Crystallographic and biochemical evidence suggest an activation mechanism where a torsional restraint on the Thr168 side chain helps drive the intramolecular processing reaction. Cleavage and formation of the active site releases the torsional restriction on Thr168, which is facilitated by a small conserved Gly-rich loop near the active site that allows the conformational changes necessary for activation.
| + | |
| | | | |
| - | Uncoupling Intramolecular Processing and Substrate Hydrolysis in the N-Terminal Nucleophile Hydrolase hASRGL1 by Circular Permutation.,Li W, Cantor JR, Yogesha SD, Yang S, Chantranupong L, Liu JQ, Agnello G, Georgiou G, Stone EM, Zhang Y ACS Chem Biol. 2012 Aug 29. PMID:22891768<ref>PMID:22891768</ref>
| + | ==See Also== |
| - | | + | *[[Asparaginase 3D structures|Asparaginase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3tkj" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Asparaginase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Li, W Z]] | + | [[Category: Li WZ]] |
| - | [[Category: Liu, J]] | + | [[Category: Liu J]] |
| - | [[Category: Yogesha, S D]] | + | [[Category: Yogesha SD]] |
| - | [[Category: Zhang, Y]] | + | [[Category: Zhang Y]] |
| - | [[Category: Alpha-beta-beta-alpha]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
