Evidence to Suggest Bacterial Lipoprotein Diacylglyceryl Transferase (Lgt) is a Weakly Associated Inner Membrane Protein

The unique and ubiquitous bacterial lipoprotein biosynthesis pathway is an attractive new antibiotic target. Crystal structures of its three biosynthetic enzymes have been solved recently. The first enzyme, Phosphatidylglycerol:proLipoprotein diacylglyceryl Transferase (Lgt), which initiates the pos...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of membrane biology 2019-12, Vol.252 (6), p.563-575
Main Authors: Sangith, Nikhil, Kumar, Subramani, Sankaran, Krishnan
Format: Article
Language:English
Subjects:
Antibiotics
Biochemistry
Biomedical and Life Sciences
Biosynthesis
Catalysis
Computer applications
Crystal structure
Docking
Helices
Human Physiology
Hydrophobicity
Life Sciences
Lipids
Membrane proteins
Phosphatidylglycerol
Phospholipids
Post-translation
Protein biosynthesis
Proteins
Proteolysis
Secretion
Software
Solubilization
Spheroplasts
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The unique and ubiquitous bacterial lipoprotein biosynthesis pathway is an attractive new antibiotic target. Crystal structures of its three biosynthetic enzymes have been solved recently. The first enzyme, Phosphatidylglycerol:proLipoprotein diacylglyceryl Transferase (Lgt), which initiates the post-translational modification at the metabolic interface of protein biosynthesis, phospholipid biosynthesis, protein secretion and lipid modification was reported to be a seven-transmembrane helical structure with a catalytic periplasmic head. Its complete solubilization in water or mild detergent in a fully active state, its chromatographic behaviour as an active monomer in the absence of detergent and recovery of active whole-length protein after proteolytic treatment of spheroplasts cast serious doubts about its proposed membrane association and orientation. Rather, it could be a seven-helical bundle partially embedded in the inner membrane’s inner leaflet aided by hydrophobic interaction. In fact, there are examples where originally reported seven-transmembrane proteins were later shown to be seven-helical peripheral membrane proteins based on solubilization criterion and re-analysis. Validated computational tool, Membrane Optimal Docking Area (MODA), also predicted a weaker association of Lgt’s helices with the membrane compared to typical transmembrane proteins. This insight is crucial to Lgt-based antibiotic design.
ISSN:0022-2631
1432-1424
DOI:10.1007/s00232-019-00076-3