Binding parameters and thermodynamics of the interaction of imino sugars with a recombinant human acid α-glucosidase (alglucosidase alfa): Insight into the complex formation mechanism

Yoshimizu, Michiru; Tajima, Youichi; Matsuzawa, Fumiko; Aikawa, Sei-ichi; Iwamoto, Kunihiko; Kobayashi, Toshihide; Edmunds, Tim; Fujishima, Kaori; Tsuji, Daisuke; Itoh, Kohji; Ikekita, Masahiko; Kawashima, Ichiro; Sugawara, Kazuki; Ohyanagi, Naho; Suzuki, Toshihiro; Togawa, Tadayasu; Ohno, Kazuki; Sakuraba, Hitoshi

doi:10.1016/j.cca.2008.02.014

Cited by 37 publications

(30 citation statements)

References 24 publications

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“…The analysis is on the basis of the geographic distances between the wild-type and substituted amino acid residues in the three-dimensional model, according the method described earlier. [19][20][21][22]25 Structural modeling of the surface region affected by representative amino acid substitutions…”

Section: Determination Of Rmsd Values Of All Atoms In Mutant Human Acmentioning

confidence: 99%

Structural modeling of mutant α-glucosidases resulting in a processing/transport defect in Pompe disease

et al. 2009

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To elucidate the mechanism underlying transport and processing defects from the viewpoint of enzyme folding, we constructed three-dimensional models of human acid a-glucosidase encompassing 27 relevant amino acid substitutions by means of homology modeling. Then, we determined in each separate case the number of affected atoms, the root-mean-square distance value and the solvent-accessible surface area value. The analysis revealed that the amino acid substitutions causing a processing or transport defect responsible for Pompe disease were widely spread over all of the five domains comprising the acid a-glucosidase. They were distributed from the core to the surface of the enzyme molecule, and the predicted structural changes varied from large to very small. Among the structural changes, we paid particular attention to G377R and G483R. These two substitutions are predicted to cause electrostatic changes in neighboring small regions on the molecular surface. The quality control system of the endoplasmic reticulum apparently detects these very small structural changes and degrades the mutant enzyme precursor (G377R), but also the cellular sorting system might be misled by these minor changes whereby the precursor is secreted instead of being transported to lysosomes (G483R).

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Section: Determination Of Rmsd Values Of All Atoms In Mutant Human Acmentioning

confidence: 99%

Structural modeling of mutant α-glucosidases resulting in a processing/transport defect in Pompe disease

et al. 2009

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“…26 In this study, we used a new structural model of the human GAA described above as a template, and predicted the structure of the complex between the mutant GAA and DNJ. AutoDock 4.0 (Molecular Graphics Laboratory, La Jolla, CA, USA), a grid-based docking program, was used to dock DNJ to the S529V mutant GAA according to the method described previously.…”

Section: Calculation Of Numbers Of Atoms Influenced By Amino Acid Submentioning

confidence: 99%

Biochemical and structural study on a S529V mutant acid α-glucosidase responsive to pharmacological chaperones

et al. 2011

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“…Ligand-based virtual screening approach was used in here to calculate the lowest binding energy between α-glucosidase enzyme with ligand and also to study their binding affinity 16 . We chose the enzyme α-glucosidase C-neutral protein in humans as the target for virtual screening [17][18][19][20][21][22][23][24] .…”

Section: Introductionmentioning

confidence: 99%

Design of Cinnamic Acid Derivatives and Molecular Docking Toward Human-Neutral a-Glucosidase by using Homology Modeling

Ernawati

Mun’im²,

Hanafi

et al. 2017

Orient. J. Chem

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Most of the biological testing of α-glucosidase inhibitors was carried out on yeast and rat intestinal. The aim of this study was to explore molecular interactions which occurred during inhibition process of human-neutral α-glucosidase by cinnamic acid derivatives. In this paper, cinnamic acid was used as the lead compound whose carboxylic acid moeity was replaced by alkyl amine against the macromolecule target which was human-neutral α-glucosidase enzyme. In order to understand the mechanism of interaction of the ligand binding conformations and to identify potent α-glucosidase inhibitor, molecular modeling studies with homology modeling method were used to investigate the problem. The structure of homology model of human α-glucosidase was built by using neutral-human α-glucosidase (GANC) with 914 amino acid residues from the Swiss-Prot with Q8TET4 identity and using the mold template of 2G3M (PDB ID). The model of enzyme was constructed based on the crystal structure of the S.solphataricus α-glucosidase, Ma1A, and human N-terminal subunit of Maltase Glucoamylase (NtMGAM). The molecular docking simulation of cinnamic acid derivatives was carried out on Autodock 4.2. Two parameters from docking simulation that can predict the inhibition activity of α-glucosidase enzyme are: low free energy Gibs and low kinetic inhibition value. The Gibs free energy value (ΔG) obtained from the docking simulation showed that 13 cinnamic acid derivatives compounds had an affinity for the receptor α-glucosidase. These compound could act as α-glucosidase inhibitor.

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Binding parameters and thermodynamics of the interaction of imino sugars with a recombinant human acid α-glucosidase (alglucosidase alfa): Insight into the complex formation mechanism

Cited by 37 publications

References 24 publications

Structural modeling of mutant α-glucosidases resulting in a processing/transport defect in Pompe disease

Structural modeling of mutant α-glucosidases resulting in a processing/transport defect in Pompe disease

Biochemical and structural study on a S529V mutant acid α-glucosidase responsive to pharmacological chaperones

Design of Cinnamic Acid Derivatives and Molecular Docking Toward Human-Neutral a-Glucosidase by using Homology Modeling

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