Automated docking to explore subsite binding by glycoside hydrolase family 6 cellobiohydrolases and endoglucanases

Mertz, Blake; Hill, Arthur V.; Mulakala, Chandrika; Reilly, Peter J.

doi:10.1002/bip.20831

Cited by 25 publications

(22 citation statements)

References 48 publications

(65 reference statements)

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“…S3) yields little additional insight in terms of the relative ligand binding free energy, it does provide further evidence for the importance of the binding affinity of the product side residues, where the interaction energy of glucose in the Ϫ2 binding site for the wild type and the four mutants is substantially greater than any other site along the tunnel. This is the same general result that Mertz et al (64) obtained using computational docking techniques. Reduction of this evaluation to either tryptophan or alanine with the glucose unit, as shown under supplemental Fig.…”

Section: Resultssupporting

confidence: 87%

Multiple Functions of Aromatic-Carbohydrate Interactions in a Processive Cellulase Examined with Molecular Simulation

Payne

Bomble

Taylor

et al. 2011

Journal of Biological Chemistry

107

117

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Background: Aromatic residues line glycoside hydrolase active sites mediating ligand binding. Results: Binding affinity is significantly altered upon tryptophan to alanine mutation, although relative to the location in the active site. Conclusion: Aromatic-carbohydrate interactions are employed in a variety of functionalities within the purview of ligand binding. Significance: Understanding the functional role of aromatic residues in the active site is necessary for the rational design of new carbohydrate-active enzymes.

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Section: Resultssupporting

confidence: 87%

Multiple Functions of Aromatic-Carbohydrate Interactions in a Processive Cellulase Examined with Molecular Simulation

Payne

Bomble

Taylor

et al. 2011

Journal of Biological Chemistry

107

117

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“…The processivity of CBHs is essential for the hydrolysis of microcrystalline cellulose (Lynd et al, 2002). Numerous experimental (Breyer and Matthews, 2001;Divne et al, 1998;Fox et al, 2012;Igarashi et al, 2009Igarashi et al, , 2011Proctor et al, 2005;Sorlie et al, 2012;Varrot et al, 2003;von Ossowski et al, 2003;Zhang et al, 2000) and computational (Bu et al, 2012;Mertz et al, 2007;Mulakala and Reilly, 2005a,b;Payne et al, 2011Payne et al, , 2012Taylor et al, 2013) studies have been carried out to understand the mechanism of processivity. The processivity has been attributed to the structural features and flexibility of the enzyme active site, or the dynamics of the ligand.…”

Section: Introductionmentioning

confidence: 99%

Cellulose chain binding free energy drives the processive move of cellulases on the cellulose surface

Wang

Zhang

Song

et al. 2016

Biotech & Bioengineering

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Processivity is essential for cellulases in their catalysis of cellulose hydrolysis. But what drives the processive move is not well understood. In this work, we use Trichoderma reesei Cel7B as a model system and show that its processivity is directly correlated to the binding free energy difference of a cellulose chain occupying the binding sites -7 to +2 and that occupying sites -7 to -1. Several mutants that have stronger interactions with glycosyl units in sites +1 and +2 than the wild type enzyme show higher processivity. The results suggest that after the release of the product cellobiose located in sites +1 and +2, the enzyme pulls the cellulose chain to fill the vacant sites, which propels its processive move on the cellulose surface. Biotechnol. Bioeng. 2016;113: 1873-1880. © 2016 Wiley Periodicals, Inc.

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“…The two loops have been demonstrated to open and close in response to ligand binding [13,14]. Eight substrate‐binding subsites from −4 to +4 are present in the active site cleft of HjeCel6A and HinCel6A [15,16]. In contrast, and despite displaying high sequence similarity to HjeCel6A and HinCel6A, the structure of the fungal endoglucanase H. insolens cellulase 6B (HinCel6B) shows that the active sites are present in a cleft formed by a C‐terminal loop deletion coupled with the peeling open of an N‐terminal loop [17].…”

Section: Introductionmentioning

confidence: 99%

Comparison of the structural changes in two cellobiohydrolases, CcCel6A and CcCel6C, from Coprinopsis cinerea – a tweezer‐like motion in the structure of CcCel6C

et al. 2012

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The basidiomycete Coprinopsis cinerea produces five cellobiohydrolases belonging to glycoside hydrolase family 6 (GH6). Among these enzymes, C. cinerea cellulase 6C (CcCel6C), but not C. cinerea cellulase 6A (CcCel6A), can efficiently hydrolyze carboxymethyl cellulose and is constitutively expressed in C. cinerea. In contrast, CcCel6A possesses a cellulose‐binding domain, and is strongly induced by cellobiose. Here, we determined the crystal structures of the CcCel6A catalytic domain complexed with a Hepes buffer molecule, with cellobiose, and with p‐nitrophenyl β‐d‐cellotrioside (pNPG3). A notable feature of the GH6 cellobiohydrolases is that the active site is enclosed by two loops to form a tunnel, and the loops have been demonstrated to open and close in response to ligand binding. The enclosed tunnel of CcCel6A–Hepes is seen as the open form, whereas the tunnels of CcCel6A–cellobiose and CcCel6A–pNPG3 adopt the closed form. pNPG3 was not hydrolyzed by CcCel6A, and bound in subsites +1 to +4. On the basis of this observation, we constructed two mutants, CcCel6A D164A and CcCel6C D102A. Neither CcCel6A D164A nor CcCel6C D102A hydrolyze phosphoric acid‐swollen cellulose. We have previously determined the crystal structures of CcCel6C unbound and in complex with ligand, both of which adopt the open form. In the present study, both CcCel6A and CcCel6C mutants were identified as the closed form. However, the motion angle of CcCel6C was more than 10‐fold greater than that of CcCel6A. The width of the active site cleft of CcCel6C was narrowed, owing to a tweezer‐like motion. Database  The coordinates and structure factors described in this article have been deposited in the Protein Data Bank under the accession codes http://www.rcsb.org/pdb/search/structidSearch.do?structureId=3VOG, http://www.rcsb.org/pdb/search/structidSearch.do?structureId=3VOH, http://www.rcsb.org/pdb/search/structidSearch.do?structureId=3VOI, http://www.rcsb.org/pdb/search/structidSearch.do?structureId=3VOJ, and http://www.rcsb.org/pdb/search/structidSearch.do?structureId=3VOF

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Automated docking to explore subsite binding by glycoside hydrolase family 6 cellobiohydrolases and endoglucanases

Cited by 25 publications

References 48 publications

Multiple Functions of Aromatic-Carbohydrate Interactions in a Processive Cellulase Examined with Molecular Simulation

Multiple Functions of Aromatic-Carbohydrate Interactions in a Processive Cellulase Examined with Molecular Simulation

Cellulose chain binding free energy drives the processive move of cellulases on the cellulose surface

Comparison of the structural changes in two cellobiohydrolases, CcCel6A and CcCel6C, from Coprinopsis cinerea – a tweezer‐like motion in the structure of CcCel6C

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