4WH1: N-acetylhexosamine 1-kinase (ligand Free)

Infant gut-associated bifidobacteria possess a metabolic pathway to utilize lacto-N-biose (Gal-beta1,3-GlcNAc) and galacto-N-biose (Gal-beta1,3-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 degrees . In the nucleotide binding site, two magnesium ions bridging the alpha-gamma and beta-gamma 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.
PDB ID: 4WH1Download
MMDB ID: 126942
PDB Deposition Date: 2014/9/19
Updated in MMDB: 2015/02
Experimental Method:
x-ray diffraction
Resolution: 2.05  Å
Source Organism:
Similar Structures:
Biological Unit for 4WH1: monomeric; determined by author and by software (PISA)
Molecular Components in 4WH1
Label Count Molecule
Protein (1 molecule)
N-acetylhexosamine 1-kinase
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

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