4GI7

Crystal structure of Klebsiella pneumoniae pantothenate kinase in complex with a pantothenate analogue

Summary for 4GI7

• Entry DOI: 10.2210/pdb4gi7/pdb
• Related: 4F7W
• Related PRD ID: PRD_000903
• Descriptor: Pantothenate kinase, ADENOSINE-5'-DIPHOSPHATE, (2R)-2,4-dihydroxy-3,3-dimethyl-N-{3-oxo-3-[(pyridin-3-ylmethyl)amino]propyl}butanamide, ... (5 entities in total)
• Functional Keywords: protein-substrate complex, transferase, structural genomics, structural genomics consortium, sgc
• Biological source: Klebsiella pneumoniae
• Cellular location: Cytoplasm (By similarity): B5XYG3
• Total number of polymer chains: 8
• Total formula weight: 312650.69

Authors

Li, B.,Tempel, W.,Smil, D.,Bolshan, Y.,Hong, B.S.,Park, H.W.,Structural Genomics Consortium (SGC) (deposition date: 2012-08-08, release date: 2013-04-10, Last modification date: 2024-02-28)

Primary citation

Li, B.,Tempel, W.,Smil, D.,Bolshan, Y.,Schapira, M.,Park, H.W.
Crystal structures of Klebsiella pneumoniae pantothenate kinase in complex with N-substituted pantothenamides.
Proteins, 81:1466-1472, 2013

PubMed Abstract: 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.

PubMed: 23553820
DOI: 10.1002/prot.24290

Experimental method

X-RAY DIFFRACTION (1.95 Å)