4GI7: Crystal Structure of Klebsiella Pneumoniae Pantothenate Kinase in Complex With a Pantothenate Analogue

N-Substituted pantothenamides are derivatives of pantothenate, the precursor in the biosynthesis of the essential metabolic cofactor coenzyme A (CoA). These compounds are substrates of pantothenate kinase (PanK) in the first step of CoA biosynthesis and possess antimicrobial activity against various pathogenic bacteria. Here we solved the crystal structure of the Klebsiella pneumoniae PanK (KpPanK) in complex with N-pentylpantothenamide (N5-Pan) to understand the molecular basis of its antimicrobial activity. The structure reveals a polar pocket interacting with the pantothenate moiety of N5-Pan and an aromatic pocket loosely protecting the pentyl tail, suggesting that the introduction of an aromatic ring to a new pantothenamide may enhance the compound's affinity to KpPanK. To test this idea, we synthesized N-pyridin-3-ylmethylpantothenamide (Np-Pan) and solved its co-crystal structure with KpPanK. The structure reveals two alternat conformations of the aromatic ring of Np-Pan bound at the aromatic pocket, providing the basis for further improvement of pantothenamide binding to KpPanK. Proteins 2013; 81:1466-1472. (c) 2013 Wiley Periodicals, Inc.
PDB ID: 4GI7Download
MMDB ID: 109017
PDB Deposition Date: 2012/8/8
Updated in MMDB: 2013/08 
Experimental Method:
x-ray diffraction
Resolution: 1.95  Å
Source Organism:
Similar Structures:
Biological Unit: dimeric; determined by software (PISA)
Molecular Components
Label Count Molecule
Proteins (2 molecules)
Pantothenate Kinase
Molecule annotation
Chemicals (16 molecules)
Molecule information is not avaliable.
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