Understanding substrate binding and the role of gatekeeping residues in PigC access tunnels.

Chem Commun (Camb)

Lehrstuhl für Biotechnologie, RWTH Aachen University, Bioeconomy Science Center (BioSC), Worringerweg 3, Aachen 52074, Germany. and DWI-Leibniz Institut für Interaktive Materialien, Forckenbeckstraße 50, Aachen 52074, Germany.

Published: March 2021

AI Article Synopsis

Article Abstract

Semi-rational redesign of the substrate binding pocket and access tunnels of prodigiosin ligase PigC enhanced the catalytic efficiency in the synthesis of pyrrolic anti-cancer agents more than 45 times. A molecular understanding was gained on residues V333 and T334 relevant to substrate binding and translocation of small pyrroles through PigC access tunnels.

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cc08226kDOI Listing

Publication Analysis

Top Keywords

substrate binding
12
access tunnels
12
pigc access
8
understanding substrate
4
binding role
4
role gatekeeping
4
gatekeeping residues
4
residues pigc
4
tunnels semi-rational
4
semi-rational redesign
4

Similar Publications

Evolution and Functional Diversification of Serine Racemase Homologs in Bacteria.

J Mol Evol

January 2025

Department of Plant and Soil Sciences, 311 Plant Science Building, University of Kentucky, Lexington, KY, 40546-0312, USA.

Amino acid racemases catalyze the interconversion of L- and D-amino acids, maintaining intracellular levels of both D- and L-amino acids. While alanine and glutamate racemases are widespread in bacteria, serine racemase (SerR) is predominantly found in animals. Recently, homologs of animal SerR were reported in some bacterial genomes, but their evolutionary distribution and functional roles remain poorly understood.

View Article and Find Full Text PDF

Transport and inhibition of the sphingosine-1-phosphate exporter SPNS2.

Nat Commun

January 2025

Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Sphingosine-1-phosphate (S1P) is a signaling lysolipid critical to heart development, immunity, and hearing. Accordingly, mutations in the S1P transporter SPNS2 are associated with reduced white cell count and hearing defects. SPNS2 also exports the S1P-mimicking FTY720-P (Fingolimod) and thereby is central to the pharmacokinetics of this drug when treating multiple sclerosis.

View Article and Find Full Text PDF

Deep eutectic solvents (DESs) have emerged as promising solvents for biocatalysis. While their impact on enzyme solvation and stabilization has been studied for several enzyme classes, their role in substrate binding is yet to be investigated. Herein, molecular dynamics (MD) simulations of horse-liver alcohol dehydrogenase (HLADH) are performed in choline chloride-ethylene glycol (ChCl-EG) and choline chloride-glycerol (ChCl-Gly) at varying water concentrations.

View Article and Find Full Text PDF

Here, we report a simple method to prepare near-IR (NIR) surface-enhanced Raman scattering (SERS) substrates by quickly freezing a citrate-capped Au nanoparticle (AuNP) solution in liquid nitrogen, followed by thawing it at room temperature. This process aggregates AuNPs in a controlled manner by forming ice crystals with smaller grain sizes when compared to a slow freezing process. The resulting smaller AuNP aggregates remain suspended in solution long enough to conduct high-throughput chemical analysis in a microwell plate using the NIR SERS spectroscopy.

View Article and Find Full Text PDF

Identification of Key Amino Acids in the A Domains of Polymyxin Synthetase Responsible for 2,4-Diaminobutyric Acid Adenylation in NBRC3020 Strain.

ACS Chem Biol

January 2025

Department of Life Science and Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya, Aichi 466-8555, Japan.

Developing novel nonribosomal peptides (NRPs) requires a comprehensive understanding of the enzymes involved in their biosynthesis, particularly the substrate amino acid recognition mechanisms in the adenylation (A) domain. This study focused on the A domain responsible for adenylating l-2,4-diaminobutyric acid (l-Dab) within the synthetase of polymyxin, an NRP produced by NBRC3020. To date, investigations into recombinant proteins that selectively adenylate l-Dab─exploring substrate specificity and enzymatic activity parameters─have been limited to reports on A domains found in enzymes synthesizing l-Dab homopolymers (pldA from USE31 and pddA from NBRC15115), which remain exceedingly rare.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!