Artur Gora

Artur Gora
Silesian University of Technology · Biotechnology Centre

PhD

About

110
Publications
21,080
Reads
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2,232
Citations
Citations since 2017
65 Research Items
1538 Citations
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Introduction
Head of the Tunneling Group. The main activity of the group lies on the border of molecular biology and computational chemistry. We are using advanced theoretical approach to investigate properties of various enzymes, to design biologically active compounds and to help experimentalist in interpretation of their results.
Additional affiliations
May 2010 - May 2013
Masaryk University
Position
  • Theoretical re-designing of access tunnels of haloalkane dehalogenases towards desired selectivity or substrate specificity
Description
  • REDEHAL project explores possibility of tunnels re-engineering in bacterial enzymes haloalkane dehalogenases. The novelty of the project lies in engineering of catalytic properties of enzymes by modification of their access tunnels.
November 2004 - November 2006
National Institute of Advanced Industrial Science and Technology
Position
  • Dehydrogenation of metylocyclohexane into toluene .
Description
  • Testing of thin alloy membrane for separation and activation of hydrogen and low temperature catalytic dehydrogenation of methylcycloheksane to toluene.
July 2002 - July 2005
Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences
Position
  • Electrochromic evacuated advanced glazing
Description
  • Electrochromic devices can find application in “smart windows” fabrication. The purpose of the research was to investigate the mechanism of WO3 layer colorizing and blanching phenomena.
Education
October 1998 - February 2002
Jagiellonian University
Field of study
  • Chemistry
October 1996 - September 1999
Jagiellonian University
Field of study
  • Molecular Biology
September 1994 - July 1998
Jagiellonian University
Field of study
  • Environmental Protection

Publications

Publications (110)
Article
Full-text available
Different methods for tunnel identification, geometry-based and small-molecule tracking approaches, were compared to provide their benefits and pitfalls. Results obtained for both crystal structures and molecular dynamics (MD) simulations were analyzed to investigate if a more computationally demanding method would be beneficial. Careful examinatio...
Article
Full-text available
The evolutionary variability of a protein’s residues is highly dependent on protein region and function. Solvent-exposed residues, excluding those at interaction interfaces, are more variable than buried residues whereas active site residues are considered to be conserved. The abovementioned rules apply also to α/β-hydrolase fold proteins—one of th...
Article
Full-text available
Congenital Disorders of Glycosylation (CDG) are multisystemic metabolic disorders showing highly heterogeneous clinical presentation, molecular etiology, and laboratory results. Here, we present different transferrin isoform patterns (obtained by isoelectric focusing) from three female patients harboring the ALG13 c.320A>G mutation. Contrary to oth...
Article
Full-text available
Based on previous large-scale in silico screening several factor Xa inhibitors were proposed to potentially inhibit SARS-CoV-2 M pro . In addition to their known anticoagulants activity this potential inhibition could have an additional therapeutic effect on patients with COVID-19 disease. In this study we examined the binding of the Apixaban, Betr...
Preprint
Full-text available
The evolutionary variability of a protein’s residues is highly dependent on protein region and function. Solvent-exposed residues, excluding those at interaction interfaces, are more variable than buried residues whereas active site residues are considered to be conserved. The abovementioned rules apply also to α/β-hydrolase fold proteins - one of...
Article
Full-text available
Enzymes with buried active sites maintain their catalytic function via a single tunnel or tunnel network. In this study we analyzed the functionality of soluble epoxide hydrolases (sEHs) tunnel network, by comparing the overall enzyme structure with the tunnel’s shape and size. sEHs were divided into three groups based on their structure and the tu...
Article
Full-text available
In the present study we tested, using the microscale thermophoresis technique, a small library of thionocarbamates, thiolocarbamates, sulfide and disulfide as potential lead compounds for SARS-CoV2 Mpro drug design. The successfully identified binder is a representative of the thionocarbamates group with a high potential for future modifications ai...
Article
Full-text available
Human soluble epoxide hydrolase (hsEH) is involved in the hydrolysis of epoxyeicosatrienoic acids (EETs), which have potent anti-inflammatory properties. Given that EET conversion generates nonbioactive molecules, inhibition of this enzyme would be beneficial. Past decades of work on hsEH inhibitors resulted in numerous potential compounds, of whic...
Data
Supplementary information for: Computational insights into the known inhibitors of human soluble epoxide hydrolase 10.1016/j.drudis.2021.05.017
Article
Full-text available
AQUA-DUCT software reverses the standard approach of the molecular dynamics simulations analysis of macromolecules, focusing on solvent, cosolvent and small ligands analysis considered as specific molecular probes instead of analysis of macromolecules atoms movement. In this article we present six basic tutorials instructing the users in the best p...
Article
Full-text available
The pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious global health threat. Since no specific therapeutics are available, researchers around the world screened compounds to inhibit various molecular targets of SARS-CoV-2 including its main protease (Mpro) essential for viral replication. Due to the high ur...
Article
Full-text available
1) Background: Molybdenum cofactor deficiency type B (MOCODB, #252160) is a rare autosomal recessive metabolic disorder characterized by intractable seizures of neonatal-onset, muscular spasticity, accompanying with hypouricemia, elevated urinary sulfite levels and craniofacial dysmorphism. Thirty-five patients were reported to date. (2) Methods: O...
Preprint
Full-text available
Human soluble epoxide hydrolase (hsEH) has been known to be involved in the hydrolysis of epoxyeicosatrienoic acids (EETs), which are anti-inflammatory and cardioprotective signalling molecules. Since the conversion of EETs into the corresponding diols generates non-bioactive molecules, the enzyme’s inhibition would be beneficial. hsEH quickly beca...
Article
Full-text available
The novel coronavirus whose outbreak took place in December 2019 continues to spread at a rapid rate worldwide. In the absence of an effective vaccine, inhibitor repurposing or de novo drug design may offer a longer-term strategy to combat this and future infections due to similar viruses. Here, we report on detailed classical and mixed-solvent mol...
Preprint
Full-text available
The novel coronavirus whose outbreak took place in December 2019 continues to spread at a rapid rate worldwide. In the absence of an effective vaccine, inhibitor repurposing or de novo design may offer a longer-term strategy to combat this and future infections due to similar viruses. Here, we report on detailed molecular dynamics simulations of th...
Article
Full-text available
The present study assesses the in vitro and in vivo bioavailability of genistein derivatives, hydroxyalkyl- and glycosyl alkyl ethers (glycoconjugates). Studies were carried out using compounds that exhibit higher in vitro antiproliferative activity in comparison with the parent isoflavone. Based on in vitro experiments using the Parallel Artificia...
Article
Full-text available
Water molecules maintain proteins’ structures, functions, stabilities and dynamics. They can occupy certain positions or pass quickly via a protein’s interior. Regardless of their behaviour, water molecules can be used for the analysis of proteins’ structural features and biochemical properties. Here, we present a list of several software programs...
Article
Full-text available
Loops are the most variable and unorganized elements of the secondary structure of proteins. Their ability to shift their shape can play a role in the binding of small ligands, enzymatic catalysis, or protein−protein interactions. Due to the loop flexibility, the positions of their residues in solved structures show the largest B-factors, or in a w...
Article
Full-text available
Motivation: Tunnels, pores, channels, pockets and cavities contribute to proteins architecture and performance. However, analysis and characteristics of transportation pathways and internal binding cavities are performed separately. We aimed to provide universal tool for analysis of proteins integral interior with access to detailed information on...
Article
Full-text available
The cupin-type phosphoglucose isomerase (PfPGI) from the hyperthermophilic archaeon Pyrococcus furiosus catalyzes the reversible isomerization of glucose-6-phosphate to fructose-6-phosphate. We investigated PfPGI using protein-engineering bioinformatics tools to select functionally-important residues based on correlated mutation analyses. A pair of...
Conference Paper
Full-text available
Limonene-1,2-epoxide hydrolase (LEH) is an enzyme which catalyzes the reaction of the hydrolysis of racemic epoxides into diols in a one-step reaction. Opening of the epoxy ring results in the formation of enantiomers. Therefore they are promising catalysts, which may replace complex and inefficient chemical syntheses. Unfortunately, LEH has an acc...
Article
Full-text available
Several different approaches are used to describe the role of protein compartments and residues in catalysis and to identify key residues suitable for the modification of the activity or selectivity of the desired enzyme. In our research, we applied a combination of molecular dynamics simulations and a water tracking approach to describe the water...
Article
Full-text available
Background Here, we present an R package for entropy/variability analysis that facilitates prompt and convenient data extraction, manipulation and visualization of protein features from multiple sequence alignments. BALCONY can work with residues dispersed across a protein sequence and map them on the corresponding alignment of homologous protein s...
Article
Full-text available
D-amino acid oxidase (DAAO) degrades D-amino acids to produce α-ketoacids, hydrogen peroxide and ammonia. DAAO has often been investigated and engineered for industrial and clinical applications. We combined information from literature with a detailed analysis of the structure to engineer mammalian DAAOs. The structural analysis was complemented wi...
Data
Enzyme specific activity (µmol/min/mg) of the purified pkDAAO and hDAAO variants measured (in two replicates) towards 19 D-amino acids and glycine substrates. Rows represent the DAAO variant, where P is pkDAAO and H is hDAAO. Columns represent the corresponding substrate used (D-Ala to D-Val). (PDF)
Data
Main parameters of tunnels in pkDAAO wild type, hDAAO wild type, hDAAO Y55A, hDAAO double mutant Y55A/L56T. Freq–frequency of tunnels identified with probe radius 0.9 during 50 ns MD simulations; Avg B–average bottleneck radius [Å], Avg L–average length [Å]. (PDF)
Data
Screening the activity of pkDAAO and hDAAO variants (4, 10, 16, 42–46 in S1 Table) containing loop deletion in combination with their corresponding Y55A and wild types. Crude cell lysates were blotted on the membrane, and the activities towards 19 D-amino acids and glycine substrates were analysed. Every panel in the figure represents the activity...
Data
Screening the activity of (Approx. 50μM purified) pkDAAO variants (4, 10, 16, 37–41 in S1 Table) on the membrane towards 19 D-amino acids and glycine substrates. Alongside the pkDAAO variants, in duplicate, an equal amount of the BL21 host cell (that lacks the expression vector, but similarly induced) was blotted to observe any background activity....
Data
Comparison of tunnels detected by CAVER (represented by lines) and water inlets (represented by small spheres) detected by AQUA-DUCT in pkDAAO wild type (A) and hDAAO wild type (B). Residues dividing tunnels are represented by stick (Y55 blue, Y224 red, Y314 yellow), protein by semitransparent cartoon), Panel on the right shows same region of the p...
Data
PCA of the all DAAO variants whose specific activity (µmol/min/mg) is measured (from S3 Table). (TIF)
Data
Screening the activity of pkDAAO variants expressed in BL21 host cells: Equal amounts of crude cell lysates blotted on a membrane. The variants 1–15 from S1 Table were designed by mutating the first and second shell residues of pkDAAO to an alanine. Each panel in S1 Fig represents the activity of all the variants towards a specific substrate (D-Ala...
Data
Screening the activity of pkDAAO wild type (Variant 16 in S1 Table) and Y55A (Variant 4 in S1 Table, which is 22 in S1 Fig) towards D-amino acids, glycine and D-amino acid analogues in crude cell lysates on the membrane (in duplicate). Equal amounts of the BL21 host cell (that lack the expression vector, but similarly induced) crude lysates were bl...
Data
Screening the activity of pkDAAO variants (4, 16, 35 and 36 in S1 Table) on the membrane towards 19 D-amino acids and glycine substrates. Alongside the pkDAAO variants (approx. 50μM purified) also containing Y55A mutation or glycine mutation to the lid loop residues, in duplicate, an equal amount of the commercially available pkDAAO wild type (Calz...
Article
Full-text available
Motivation:The identification and tracking of molecules which enter active site cavity requires screening the positions of thousands of single molecules along several thousand molecular dynamic steps. To fill the existing gap between tools searching for tunnels and pathways and advanced tools employed for accelerated water flux investigations, we h...
Article
Transport of ligands between buried active sites and bulk solvent is a key step in the catalytic cycle of many enzymes. Absence of evolutionary optimized transport tunnels is an important barrier limiting the efficiency of biocatalysts prepared by computational design. Creating a structurally defined and functional ?hole? into the protein represent...
Article
Full-text available
The transport of ligands, ions or solvent molecules into proteins with buried binding sites or through the membrane is enabled by protein tunnels and channels. CAVER Analyst is a software tool for calculation, analysis and real-time visualization of access tunnels and channels in static and dynamic protein structures. It provides an intuitive graph...
Patent
Full-text available
Thermostabilization of a protein where the protein contains access routes and wherein at least one amino acid in the bottleneck of the access route is mutated, includes identifying the amino acids of the bottleneck and the amino acids control exchange of the solvent between a buried protein core and surrounding environment and/or in the packing of...
Article
The dynamic motion of enzymes during catalytic events is one of the many aspects of protein chemistry that are currently insufficiently well understood. On one hand, proteins need to have well-defined and organized structures in order to maintain stable functionality in the intracellular environment. On the other hand, some degree of flexibility is...
Article
Haloalkane dehalogenases catalyse the hydrolysis of carbon-halogen bonds in various chlorinated, brominated and iodinated compounds. These enzymes have a conserved pair of halide-stabilising residues that are important in substrate binding and stabilisation of the transition state and the halide ion product via hydrogen bonding. In all previously k...
Article
Full-text available
Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new...
Data
Full-text available
Analysis of crystal structures of DhaA. (PDF)
Data
Full-text available
Comparison of pathways calculated by CAVER 3.0, MOLE 1.2 and MolAxis 1.4. (PDF)
Data
Full-text available
Comparison of characteristics of the DhaA p1 tunnel obtained by the analysis of the molecular dynamics trajectory and crystal structures. (PDF)
Data
Clusters of pathways calculated in the molecular dynamics simulation of haloalkane dehalogenase DhaA by CAVER 3.0 (A–C) and MOLE 1.2 (D–F)