Towards Computationally Guided Design and Engineering of a Neisseria meningitidis Serogroup W Capsule Polymerase with Altered Substrate Specificity
Year: 2021
Type: article
Abstract: Heavy metal contamination of drinking water is a public health concern that requires the development of more efficient bioremediation techniques. Absorption technologies, including biosorption, provide opportunities for improvements to increase the diversity of metal ions removed and overall binding capacity. Microorganisms are a key component in wastewater treatment plants and they naturally bind metal ions through surface macromolecules but with limited capacity. The long-term goal of this work is to engineer capsule polymerases to synthesize molecules with novel functionalities. In previously published work, we showed that the Neisseria meningitidis serogroup W (NmW) galactose-sialic acid (Gal—NeuNAc) heteropolysaccharide binds lead effectively, thereby demonstrating the potential for using this capsular polysaccharide in environmental decontamination applications. In this study, computational analysis of the NmW capsule polymerase galactosyltransferase (GT) domain was used to gain insight into how the enzyme could be modified to enable the synthesis N-acetylgalactosamine-sialic acid (GalNAc—NeuNAc) heteropolysaccharide. Various computational approaches, including molecular modeling with I-TASSER and molecular dynamics simulations (MD) with NAMD, were utilized to identify key amino acid residues in the substrate binding pocket of the GT domain that may be key to conferring UDP-GalNAc specificity. Through these combined strategies and using BshA, a UDP-GlcNAc transferase, as a structural template, several NmW active site residues were identified as mutational targets to accommodate the proposed N-acetyl group in UDP-GalNAc. Thus, a rational approach for potentially conferring new properties to bacterial capsular polysaccharides is demonstrated.
Source: Processes
DOI: 10.3390/pr9122192
Institution: Morgan State University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $2,160
Awards: G179862484, G1958647014, G3226045097, XSEDE 2.0: Integrating, Enabling and Enhancing National Cyberinfrastructure with Expanding Community Involvement, G4005964189, G4803218828, G5135655433, G6056929667, G7400298905, Excellence in Research: Elucidating Factors that Affect Substrate Promiscuity of Bacterial Capsule Polymerases for Synthesis of Novel Polysaccharides, G8423653713, ASCEND Training Model to Increase Diversity in the Biomedical Research Workforce
OpenAlex ID: W4226513683