Structure of α-carbonic anhydrase from the human pathogen<i>Helicobacter pylori</i>

Compostella, Maria Elena; Berto, Paola; Vallese, Francesca; Zanotti, Giuseppe

doi:10.1107/s2053230x15010407

Cited by 15 publications

(7 citation statements)

References 35 publications

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“…The a-CA was shown to possess a periplasmic localization, the b-CA has been found in the cytoplasm, whereas no information is available on the expression/localization of the g-CA from this pathogenic bacterium 3,4,15,58,59 . It was suggested that the activity of periplasmic a-and b-CAs could be an additional requirement for the gastric colonization of the bacterium 57,60,61 . We want stress the fact that the primary sequence of the b-CA (HpyCAb) identified in the genome of H. pylori did not show a signal peptide at its N-terminal region when subject to the automated identification of the predicted signal peptide.…”

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confidence: 99%

New light on bacterial carbonic anhydrases phylogeny based on the analysis of signal peptide sequences

Supuran

Capasso

2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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Among protein families, carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes characterized by a common reaction mechanism in all life domains: the carbon dioxide hydration to bicarbonate and protons (CO 2 +H 2 O () HCO 3 À +H + ). Six genetically distinct CA families are known to date, the a-, b-, g-, d-, z-and Z-CAs. The last CA class was recently discovered analyzing the amino acid sequences of CAs from Plasmodia. Bacteria encode for enzymes belonging to the a-, b-, and g-CA classes and recently, phylogenetic analysis revealed an interesting relationship regarding the evolution of bacterial CA classes. This result evidenced that the three bacterial CA classes, in spite of the high level of the structural similarity, are evolutionarily distinct, but we noted that the primary structure of some b-CAs identified in the genome of Gram-negative bacteria present a pre-sequence of 18 or more amino acid residues at the N-terminal part. These observations and subsequent phylogenetic data presented here prompted us to propose that the b-CAs found in Gram-negative bacteria with a periplasmic space and characterized by the presence of a signal peptide might have a periplasmic localization and a role similar to that described previously for the a-CAs.

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confidence: 99%

New light on bacterial carbonic anhydrases phylogeny based on the analysis of signal peptide sequences

Supuran

Capasso

2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Docking and molecular dynamic (MD) simulations were performed to study the binding mode of carvacrol and thymol in the active site of the α- and β-CA of Helicobacter pylori (HpCAα and HpCAβ) and β-CA of Malassezia globosa (MgCA). While the 3D coordinates of HpCAα (PDB 4XFW) [ 37 ] are available in the protein data bank, the X-ray solved structure of HpCAβ is not. Thus, comparative modelling was used to build a structural model based upon the known 3D coordinates of type I β-CAs from Synechocystis sp.…”

Section: Resultsmentioning

confidence: 99%

Selective Inhibition of Helicobacter pylori Carbonic Anhydrases by Carvacrol and Thymol Could Impair Biofilm Production and the Release of Outer Membrane Vesicles

Grande

Carradori

Puca

et al. 2021

IJMS

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Helicobacter pylori, a Gram-negative neutrophilic pathogen, is the cause of chronic gastritis, peptic ulcers, and gastric cancer in humans. Current therapeutic regimens suffer from an emerging bacterial resistance rate and poor patience compliance. To improve the discovery of compounds targeting bacterial alternative enzymes or essential pathways such as carbonic anhydrases (CAs), we assessed the anti-H. pylori activity of thymol and carvacrol in terms of CA inhibition, isoform selectivity, growth impairment, biofilm production, and release of associated outer membrane vesicles-eDNA. The microbiological results were correlated by the evaluation in vitro of H. pylori CA inhibition, in silico analysis of the structural requirements to display such isoform selectivity, and the assessment of their limited toxicity against three probiotic species with respect to amoxicillin. Carvacrol and thymol could thus be considered as new lead compounds as alternative H. pylori CA inhibitors or to be used in association with current drugs for the management of H. pylori infection and limiting the spread of antibiotic resistance.

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“…Coordinating His residues were all within the expected bond length of 2.2 Å to Zn 2+ [89]. The active site appeared to be open and accessible to the solvent as observed in most CAs, with the catalytic pocket extending from the outside of the protein to the metal ion [34,90,91]. Validation results from various programs revealed that the structures modelled were of good quality (Table S5).…”

Section: Calculations Of Dimeric Models Of α-Cas and Their Validation Yields Good Quality Structuresmentioning

confidence: 85%

Alpha-Carbonic Anhydrases from Hydrothermal Vent Sources as Potential Carbon Dioxide Sequestration Agents: In Silico Sequence, Structure and Dynamics Analyses

Manyumwa

Emameh

Bishop

2020

IJMS

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With the increase in CO2 emissions worldwide and its dire effects, there is a need to reduce CO2 concentrations in the atmosphere. Alpha-carbonic anhydrases (α-CAs) have been identified as suitable sequestration agents. This study reports the sequence and structural analysis of 15 α-CAs from bacteria, originating from hydrothermal vent systems. Structural analysis of the multimers enabled the identification of hotspot and interface residues. Molecular dynamics simulations of the homo-multimers were performed at 300 K, 363 K, 393 K and 423 K to unearth potentially thermostable α-CAs. Average betweenness centrality (BC) calculations confirmed the relevance of some hotspot and interface residues. The key residues responsible for dimer thermostability were identified by comparing fluctuating interfaces with stable ones, and were part of conserved motifs. Crucial long-lived hydrogen bond networks were observed around residues with high BC values. Dynamic cross correlation fortified the relevance of oligomerization of these proteins, thus the importance of simulating them in their multimeric forms. A consensus of the simulation analyses used in this study suggested high thermostability for the α-CA from Nitratiruptor tergarcus. Overall, our novel findings enhance the potential of biotechnology applications through the discovery of alternative thermostable CO2 sequestration agents and their potential protein design.

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Structure of α-carbonic anhydrase from the human pathogenHelicobacter pylori

Cited by 15 publications

References 35 publications

New light on bacterial carbonic anhydrases phylogeny based on the analysis of signal peptide sequences

New light on bacterial carbonic anhydrases phylogeny based on the analysis of signal peptide sequences

Selective Inhibition of Helicobacter pylori Carbonic Anhydrases by Carvacrol and Thymol Could Impair Biofilm Production and the Release of Outer Membrane Vesicles

Alpha-Carbonic Anhydrases from Hydrothermal Vent Sources as Potential Carbon Dioxide Sequestration Agents: In Silico Sequence, Structure and Dynamics Analyses

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