6rwf: Difference between revisions
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The | ==The dissociation mechanism of processive cellulases== | ||
<StructureSection load='6rwf' size='340' side='right'caption='[[6rwf]], [[Resolution|resolution]] 1.64Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6rwf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Trichoderma_reesei_QM6a Trichoderma reesei QM6a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RWF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RWF FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.64Å</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=6rwf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rwf OCA], [https://pdbe.org/6rwf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rwf RCSB], [https://www.ebi.ac.uk/pdbsum/6rwf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rwf ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/G0RVK1_HYPJQ G0RVK1_HYPJQ] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cellulase enzymes deconstruct recalcitrant cellulose into soluble sugars, making them a biocatalyst of biotechnological interest for use in the nascent lignocellulosic bioeconomy. Cellobiohydrolases (CBHs) are cellulases capable of liberating many sugar molecules in a processive manner without dissociating from the substrate. Within the complete processive cycle of CBHs, dissociation from the cellulose substrate is rate limiting, but the molecular mechanism of this step is unknown. Here, we present a direct comparison of potential molecular mechanisms for dissociation via Hamiltonian replica exchange molecular dynamics of the model fungal CBH, Trichoderma reesei Cel7A. Computational rate estimates indicate that stepwise cellulose dethreading from the binding tunnel is 4 orders of magnitude faster than a clamshell mechanism, in which the substrate-enclosing loops open and release the substrate without reversing. We also present the crystal structure of a disulfide variant that covalently links substrate-enclosing loops on either side of the substrate-binding tunnel, which constitutes a CBH that can only dissociate via stepwise dethreading. Biochemical measurements indicate that this variant has a dissociation rate constant essentially equivalent to the wild type, implying that dethreading is likely the predominant mechanism for dissociation. | |||
The dissociation mechanism of processive cellulases.,Vermaas JV, Kont R, Beckham GT, Crowley MF, Gudmundsson M, Sandgren M, Stahlberg J, Valjamae P, Knott BC Proc Natl Acad Sci U S A. 2019 Oct 30. pii: 1913398116. doi:, 10.1073/pnas.1913398116. PMID:31666327<ref>PMID:31666327</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Knott | <div class="pdbe-citations 6rwf" style="background-color:#fffaf0;"></div> | ||
[[Category: Stahlberg | |||
==See Also== | |||
*[[Glucanase 3D structures|Glucanase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Trichoderma reesei QM6a]] | |||
[[Category: Knott BC]] | |||
[[Category: Stahlberg J]] | |||
Latest revision as of 15:30, 24 January 2024
The dissociation mechanism of processive cellulasesThe dissociation mechanism of processive cellulases
Structural highlights
FunctionPublication Abstract from PubMedCellulase enzymes deconstruct recalcitrant cellulose into soluble sugars, making them a biocatalyst of biotechnological interest for use in the nascent lignocellulosic bioeconomy. Cellobiohydrolases (CBHs) are cellulases capable of liberating many sugar molecules in a processive manner without dissociating from the substrate. Within the complete processive cycle of CBHs, dissociation from the cellulose substrate is rate limiting, but the molecular mechanism of this step is unknown. Here, we present a direct comparison of potential molecular mechanisms for dissociation via Hamiltonian replica exchange molecular dynamics of the model fungal CBH, Trichoderma reesei Cel7A. Computational rate estimates indicate that stepwise cellulose dethreading from the binding tunnel is 4 orders of magnitude faster than a clamshell mechanism, in which the substrate-enclosing loops open and release the substrate without reversing. We also present the crystal structure of a disulfide variant that covalently links substrate-enclosing loops on either side of the substrate-binding tunnel, which constitutes a CBH that can only dissociate via stepwise dethreading. Biochemical measurements indicate that this variant has a dissociation rate constant essentially equivalent to the wild type, implying that dethreading is likely the predominant mechanism for dissociation. The dissociation mechanism of processive cellulases.,Vermaas JV, Kont R, Beckham GT, Crowley MF, Gudmundsson M, Sandgren M, Stahlberg J, Valjamae P, Knott BC Proc Natl Acad Sci U S A. 2019 Oct 30. pii: 1913398116. doi:, 10.1073/pnas.1913398116. PMID:31666327[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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