5nx8: Difference between revisions
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<StructureSection load='5nx8' size='340' side='right' caption='[[5nx8]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='5nx8' size='340' side='right' caption='[[5nx8]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5nx8]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NX8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NX8 FirstGlance]. <br> | <table><tr><td colspan='2'>[[5nx8]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Feldhofer_1 Feldhofer 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NX8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NX8 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenylosuccinate_lyase Adenylosuccinate lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.2.2 4.3.2.2] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenylosuccinate_lyase Adenylosuccinate lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.2.2 4.3.2.2] </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=5nx8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nx8 OCA], [http://pdbe.org/5nx8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nx8 RCSB], [http://www.ebi.ac.uk/pdbsum/5nx8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nx8 ProSAT]</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=5nx8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nx8 OCA], [http://pdbe.org/5nx8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nx8 RCSB], [http://www.ebi.ac.uk/pdbsum/5nx8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nx8 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The availability of genomic data from extinct homini such as Neanderthals has caused a revolution in palaeontology allowing the identification of modern human-specific protein substitutions. Currently, little is known as to how these substitutions alter the proteins on a molecular level. Here, we investigate adenylosuccinate lyase, a conserved enzyme involved in purine metabolism for which several substitutions in the modern human protein (hADSL) have been described to affect intelligence and behaviour. During evolution, modern humans acquired a specific substitution (Ala429Val) in ADSL distinguishing it from the ancestral variant present in Neanderthals (nADSL). We show here that despite this conservative substitution being solvent exposed and located distant from the active site, there is a difference in thermal stability, but not enzymology or ligand binding between nADSL and hADSL. Substitutions near residue 429 which do not profoundly affect enzymology were previously reported to cause neurological symptoms in humans. This study also reveals that ADSL undergoes conformational changes during catalysis which, together with the crystal structure of a hitherto undetermined product bound conformation, explains the molecular origin of disease for several modern human ADSL mutants. | |||
Molecular comparison of Neanderthal and Modern Human adenylosuccinate lyase.,Van Laer B, Kapp U, Soler-Lopez M, Moczulska K, Paabo S, Leonard G, Mueller-Dieckmann C Sci Rep. 2018 Dec 20;8(1):18008. doi: 10.1038/s41598-018-36195-5. PMID:30573755<ref>PMID:30573755</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5nx8" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Adenylosuccinate lyase]] | [[Category: Adenylosuccinate lyase]] | ||
[[Category: Feldhofer 1]] | |||
[[Category: Kapp, U]] | [[Category: Kapp, U]] | ||
[[Category: Laer, B Van]] | [[Category: Laer, B Van]] | ||
Revision as of 12:21, 30 January 2019
Crystal structure of Neanderthal Adenylosuccinate Lyase (ADSL)Crystal structure of Neanderthal Adenylosuccinate Lyase (ADSL)
Structural highlights
Publication Abstract from PubMedThe availability of genomic data from extinct homini such as Neanderthals has caused a revolution in palaeontology allowing the identification of modern human-specific protein substitutions. Currently, little is known as to how these substitutions alter the proteins on a molecular level. Here, we investigate adenylosuccinate lyase, a conserved enzyme involved in purine metabolism for which several substitutions in the modern human protein (hADSL) have been described to affect intelligence and behaviour. During evolution, modern humans acquired a specific substitution (Ala429Val) in ADSL distinguishing it from the ancestral variant present in Neanderthals (nADSL). We show here that despite this conservative substitution being solvent exposed and located distant from the active site, there is a difference in thermal stability, but not enzymology or ligand binding between nADSL and hADSL. Substitutions near residue 429 which do not profoundly affect enzymology were previously reported to cause neurological symptoms in humans. This study also reveals that ADSL undergoes conformational changes during catalysis which, together with the crystal structure of a hitherto undetermined product bound conformation, explains the molecular origin of disease for several modern human ADSL mutants. Molecular comparison of Neanderthal and Modern Human adenylosuccinate lyase.,Van Laer B, Kapp U, Soler-Lopez M, Moczulska K, Paabo S, Leonard G, Mueller-Dieckmann C Sci Rep. 2018 Dec 20;8(1):18008. doi: 10.1038/s41598-018-36195-5. PMID:30573755[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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