4NE2

Pantothenamide-bound Pantothenate Kinase from Klebsiella pneumoniae

Summary for 4NE2

• Entry DOI: 10.2210/pdb4ne2/pdb
• Related: 4NB4
• Descriptor: Pantothenate kinase, ADENOSINE-5'-DIPHOSPHATE, (R)-N-(3-((2-(benzo[d][1,3]dioxol-5-yl)ethyl)amino)-3-oxopropyl)-2,4-dihydroxy-3,3-dimethylbutanamide, ... (5 entities in total)
• Functional Keywords: protein-substrate complex, transferase
• Biological source: Klebsiella pneumoniae
• Cellular location: Cytoplasm (By similarity): B5XYG3
• Total number of polymer chains: 2
• Total formula weight: 78557.40

Authors

Hughes, S.J.,Antoshchenko, T.,Kim, K.P.,Smil, D.,Park, H.W. (deposition date: 2013-10-28, release date: 2014-02-26, Last modification date: 2023-09-20)

Primary citation

Hughes, S.J.,Antoshchenko, T.,Kim, K.P.,Smil, D.,Park, H.W.
Structural characterization of a new N-substituted pantothenamide bound to pantothenate kinases from Klebsiella pneumoniae and Staphylococcus aureus.
Proteins, 82:1542-1548, 2014

PubMed Abstract: Pantothenate kinase (PanK) is the rate-limiting enzyme in Coenzyme A biosynthesis, catalyzing the ATP-dependent phosphorylation of pantothenate. We solved the co-crystal structures of PanKs from Staphylococcus aureus (SaPanK) and Klebsiella pneumonia (KpPanK) with N-[2-(1,3-benzodioxol-5-yl)ethyl] pantothenamide (N354-Pan). Two different N354-Pan conformers interact with polar/nonpolar mixed residues in SaPanK and aromatic residues in KpPanK. Additionally, phosphorylated N354-Pan is found at the closed active site of SaPanK but not at the open active site of KpPanK, suggesting an exchange of the phosphorylated product with a new N354-Pan only in KpPanK. Together, pantothenamides conformational flexibility and binding pocket are two key considerations for selective compound design.

PubMed: 24470271
DOI: 10.1002/prot.24524

Experimental method

X-RAY DIFFRACTION (1.9 Å)