Lysine biosynthesis in bacteria: a metallodesuccinylase as a potential antimicrobial target

• Published in: Journal of biological inorganic chemistry Vol. 18; no. 2; pp. 155 - 163
• Main Authors: Gillner, Danuta M., Becker, Daniel P., Holz, Richard C.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-02-2013
• Subjects: Amidohydrolases - antagonists & inhibitors; Amidohydrolases - chemistry; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Bacteria - drug effects; Bacteria - enzymology; Bacterial Proteins - antagonists & inhibitors; Bacterial Proteins - chemistry; Biochemistry; Biomedical and Life Sciences; Catalytic Domain; Drug Resistance, Bacterial; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Humans; Life Sciences; Lysine - biosynthesis; Microbiology; Minireview; Models, Molecular; Protein Binding; X-ray crystallography; Metallohydrolase; DapE; Antibiotics; Inhibitor design; Zinc; Catalytic mechanism
• ISSN: 0949-8257; 1432-1327
• DOI: 10.1007/s00775-012-0965-1

In this review, we summarize the recent literature on
dapE
-encoded
N
-succinyl-
l
,
l
-diaminopimelic acid desuccinylase (DapE) enzymes, with an emphasis on structure–function studies that provide insight into the catalytic mechanism. Crystallographic data have also provided insight into residues that might be involved in substrate and hence inhibitor recognition and binding. These data have led to the design and synthesis of several new DapE inhibitors, which are described along with what is known about how inhibitors interact with the active site of DapE enzymes, including the efficacy of a moderately strong DapE inhibitor.
Graphical abstract