4WH1

N-Acetylhexosamine 1-kinase (ligand free)

Summary for 4WH1

• Entry DOI: 10.2210/pdb4wh1/pdb
• Related: 4OCJ 4OCO 4OCP 4OCQ 4OCU 4OCV 4WH2 4WH3
• Descriptor: N-acetylhexosamine 1-kinase, GLYCEROL, ACETIC ACID, ... (4 entities in total)
• Functional Keywords: nahk, anomeric kinase, aph, open conformation, transferase
• Biological source: Bifidobacterium longum subsp. longum JCM 1217
• Total number of polymer chains: 1
• Total formula weight: 41150.04

Authors

Sato, M.,Arakawa, T.,Nam, Y.W.,Nishimoto, M.,Kitaoka, M.,Fushinobu, S. (deposition date: 2014-09-19, release date: 2015-02-11, Last modification date: 2024-03-20)

Primary citation

Sato, M.,Arakawa, T.,Nam, Y.W.,Nishimoto, M.,Kitaoka, M.,Fushinobu, S.
Open-close structural change upon ligand binding and two magnesium ions required for the catalysis of N-acetylhexosamine 1-kinase
Biochim.Biophys.Acta, 1854:333-340, 2015

PubMed Abstract: Infant gut-associated bifidobacteria possess a metabolic pathway to utilize lacto-N-biose (Gal-β1,3-GlcNAc) and galacto-N-biose (Gal-β1,3-GalNAc) from human milk and glycoconjugates specifically. In this pathway, N-acetylhexosamine 1-kinase (NahK) catalyzes the phosphorylation of GlcNAc or GalNAc at the anomeric C1 position with ATP. Crystal structures of NahK have only been determined in the closed state. In this study, we determined open state structures of NahK in three different forms (apo, ADP complex, and ATP complex). A comparison of the open and closed state structures revealed an induced fit structural change defined by two rigid domains. ATP binds to the small N-terminal domain, and binding of the N-acetylhexosamine substrate to the large C-terminal domain induces a closing conformational change with a rotation angle of 16°. In the nucleotide binding site, two magnesium ions bridging the α-γ and β-γ phosphates were identified. A mutational analysis indicated that a residue coordinating both of the two magnesium ions (Asp228) is essential for catalysis. The involvement of two magnesium ions in the catalytic machinery is structurally similar to the catalytic structures of protein kinases and aminoglycoside phosphotransferases, but distinct from the structures of other anomeric kinases or sugar 6-kinases. These findings help to elucidate the possible evolutionary adaptation of substrate specificities and induced fit mechanism.

PubMed: 25644306
DOI: 10.1016/j.bbapap.2015.01.011

Experimental method

X-RAY DIFFRACTION (2.05 Å)