JBIC Journal of Biological Inorganic Chemistry

, Volume 18, Issue 2, pp 155–163 | Cite as

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

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Abstract

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

Keywords

DapE Metallohydrolase Antibiotics Zinc X-ray crystallography Inhibitor design Catalytic mechanism 

Abbreviations

AAP

Aminopeptidase from Vibrio proteolyticus (Aeromonas proteolytica)

CEPA

2-Carboxyethylphosphonic acid

CPG2

Carboxypeptidase G2 from Pseudomonas sp. strain RS-16

DapE

dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase

EPR

Electron paramagnetic resonance

EXAFS

Extended X-ray absorption fine structure

l,l-SDAP

N-Succinyl-l,l-diaminopimelic acid

LPA

l-Leucine phosphonic acid

m-DAP

meso-Diaminopimelate

MSPA

5-Mercaptopentanoic acid

SDAP

N-Succinyldiaminopimelic acid

Notes

Acknowledgments

This work was supported by the National Institutes of Health (R15 AI085559-01A1, R.C.H.).

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Copyright information

© SBIC 2012

Authors and Affiliations

  1. 1.Department of Chemistry and BiochemistryLoyola University-ChicagoChicagoUSA
  2. 2.Department of ChemistrySilesian University of TechnologyGliwicePoland

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