3V8R: Crystal structure of NAD kinase 1 H223E mutant from Listeria monocytogenes in complex with 5'-amino-8-bromo-5'-deoxyadenosine

Making new ligands for a given protein by in situ ligation of building blocks (or fragments) is an attractive method. However, it suffers from inherent limitations, such as the limited number of available chemical reactions and the low information content of usual chemical library deconvolution. Here, we describe a focused screening of adenosine derivatives using X-ray crystallography. We discovered an unexpected and biocompatible chemical reactivity and have simultaneously identified the mode of binding of the resulting products. We observed that the NAD kinase from Listeria monocytogenes (LmNADK1) can promote amide formation between 5'-amino-5'-deoxyadenosine and carboxylic acid groups. This unexpected reactivity allowed us to bridge in situ two adenosine derivatives to fully occupy the active NAD site. This guided the design of a close analog showing micromolar inhibition of two human pathogenic NAD kinases and potent bactericidal activity against Staphylococcus aureus in vitro.
PDB ID: 3V8RDownload
MMDB ID: 98008
PDB Deposition Date: 2011/12/23
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.39  Å
Source Organism:
Similar Structures:
Biological Unit for 3V8R: dimeric; determined by software (PISA)
Molecular Components in 3V8R
Label Count Molecule
Proteins (2 molecules)
Probable Inorganic Polyphosphate/atp-nad Kinase 1(Gene symbol: ppnK)
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB