3PYL: Crystal Structure Of Aspartate Beta-semialdehide Dehydrogenase From Streptococcus Pneumoniae With D-2,3-diaminopropionate

Citation:
Abstract
The aspartate biosynthetic pathway provides essential metabolites for many important biological functions, including the production of four essential amino acids. As this critical pathway is only present in plants and microbes, any disruptions will be fatal to these organisms. An early pathway enzyme, l-aspartate-beta-semialdehyde dehydrogenase, produces a key intermediate at the first branch point of this pathway. Developing potent and selective inhibitors against several orthologs in the l-aspartate-beta-semialdehyde dehydrogenase family can serve as lead compounds for antibiotic development. Kinetic studies of two small molecule fragment libraries have identified inhibitors that show good selectivity against l-aspartate-beta-semialdehyde dehydrogenases from two different bacterial species, Streptococcus pneumoniae and Vibrio cholerae, despite the presence of an identical constellation of active site amino acids in this homologous enzyme family. Structural characterization of enzyme-inhibitor complexes have elucidated different modes of binding between these structurally related enzymes. This information provides the basis for a structure-guided approach to the development of more potent and more selective inhibitors.
PDB ID: 3PYLDownload
MMDB ID: 96206
PDB Deposition Date: 2010/12/13
Updated in MMDB: 2014/10
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 3PYL: dimeric; determined by author and by software (PISA)
Molecular Components in 3PYL
Label Count Molecule
Proteins (2 molecules)
2
Aspartate-semialdehyde Dehydrogenase
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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