Crystallographic Study of Peptidoglycan Biosynthesis Enzyme MurD: Domain Movement Revisited

The biosynthetic pathway of peptidoglycan, an essential component of bacterial cell wall, is a well-recognized target for antibiotic development. Peptidoglycan precursors are synthesized in the bacterial cytosol by various enzymes including the ATP-hydrolyzing Mur ligases, which catalyze the stepwis...

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Published in:PloS one 2016-03, Vol.11 (3), p.e0152075-e0152075
Main Authors: Šink, Roman, Kotnik, Miha, Zega, Anamarija, Barreteau, Hélène, Gobec, Stanislav, Blanot, Didier, Dessen, Andréa, Contreras-Martel, Carlos
Format: Article
Language:English
Subjects:
Amino acids
Analysis
Antibacterial agents
Antibiotics
ATP
Bacteria
Bacterial cell walls
Binding
Binding sites
Biochemistry, Molecular Biology
Biology and Life Sciences
Biomaterials
Biosynthesis
Care and treatment
Cell walls
Conformation
Crystal structure
Crystallography
Crystallography, X-Ray
Cytosol
E coli
Enzymes
Escherichia coli
Escherichia coli - enzymology
Experiments
Glutamic acid
Health aspects
Life Sciences
Ligands
Medicine and Health Sciences
Peptide Synthases - chemistry
Peptide Synthases - metabolism
Peptides
Peptidoglycan - biosynthesis
Peptidoglycan - chemistry
Peptidoglycans
Pharmacy
Physical Sciences
Protein Structure, Tertiary
Proteins
Research and Analysis Methods
Structural Biology
Studies
Substrates
Target recognition
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cited_by cdi_FETCH-LOGICAL-c792t-31aca6f4c878c8b285f89c56fa94ca71e1593405e05065441617bfbd37a157c63
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container_issue 3
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container_title PloS one
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creator Šink, Roman
Kotnik, Miha
Zega, Anamarija
Barreteau, Hélène
Gobec, Stanislav
Blanot, Didier
Dessen, Andréa
Contreras-Martel, Carlos
description The biosynthetic pathway of peptidoglycan, an essential component of bacterial cell wall, is a well-recognized target for antibiotic development. Peptidoglycan precursors are synthesized in the bacterial cytosol by various enzymes including the ATP-hydrolyzing Mur ligases, which catalyze the stepwise addition of amino acids to a UDP-MurNAc precursor to yield UDP-MurNAc-pentapeptide. MurD catalyzes the addition of D-glutamic acid to UDP-MurNAc-L-Ala in the presence of ATP; structural and biochemical studies have suggested the binding of the substrates with an ordered kinetic mechanism in which ligand binding inevitably closes the active site. In this work, we challenge this assumption by reporting the crystal structures of intermediate forms of MurD either in the absence of ligands or in the presence of small molecules. A detailed analysis provides insight into the events that lead to the closure of MurD and reveals that minor structural modifications contribute to major overall conformation alterations. These novel insights will be instrumental in the development of new potential antibiotics designed to target the peptidoglycan biosynthetic pathway.
doi_str_mv 10.1371/journal.pone.0152075
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1932-6203
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subjects Amino acids
Analysis
Antibacterial agents
Antibiotics
ATP
Bacteria
Bacterial cell walls
Binding
Binding sites
Biochemistry, Molecular Biology
Biology and Life Sciences
Biomaterials
Biosynthesis
Care and treatment
Cell walls
Conformation
Crystal structure
Crystallography
Crystallography, X-Ray
Cytosol
E coli
Enzymes
Escherichia coli
Escherichia coli - enzymology
Experiments
Glutamic acid
Health aspects
Life Sciences
Ligands
Medicine and Health Sciences
Peptide Synthases - chemistry
Peptide Synthases - metabolism
Peptides
Peptidoglycan - biosynthesis
Peptidoglycan - chemistry
Peptidoglycans
Pharmacy
Physical Sciences
Protein Structure, Tertiary
Proteins
Research and Analysis Methods
Structural Biology
Studies
Substrates
Target recognition
title Crystallographic Study of Peptidoglycan Biosynthesis Enzyme MurD: Domain Movement Revisited
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