4mo4

Crystal structure of AnmK bound to AMPPCP

spinqualitylabelsall models 4mo4, resolution 1.67Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4mo4 is a 4 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.67Å Ligands: ACP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ANMK_PSEAE Catalyzes the specific phosphorylation of 1,6-anhydro-N-acetylmuramic acid (anhMurNAc) with the simultaneous cleavage of the 1,6-anhydro ring, generating MurNAc-6-P. Is required for the utilization of anhMurNAc either imported from the medium or derived from its own cell wall murein, and thus plays a role in cell wall recycling (By similarity). Publication Abstract from PubMed Anhydro-sugar kinases are unique from other sugar kinases in that they must cleave the 1,6-anhydro ring of their sugar substrate in order to phosphorylate it using ATP. Here we show that the peptidoglycan recycling enzyme 1,6-Anhydro-N-acetylmuramic acid kinase (AnmK) from Pseudomonas aeruginosa undergoes large conformational changes during its catalytic cycle, with its two domains rotating apart by up to 32 degrees around two hinge regions to expose an active site cleft into which the substrates 1,6-anhydroMurNAc and ATP can bind. X-ray structures of the open state bound to a nonhydrolyzable ATP analogue (AMPPCP) and 1,6-anhydroMurNAc provides detailed insight into a ternary complex that forms preceding an operative Michaelis complex. Structural analysis of the hinge regions demonstrates a role for nucleotide binding and possible cross-talk between the bound ligands to modulate the opening and closing of AnmK. Though AnmK was found to exhibit similar binding affinities for ATP, ADP and AMPPCP according to fluorescence spectroscopy, SAXS analyses revealed that AnmK adopts an open conformation in solution in the absence of ligand, and that it remains in this open state after binding AMPPCP, as we had observed for our crystal structure of this complex. In contrast, the enzyme favoured a closed conformation when bound to ADP in solution, consistent with a previous crystal structure of this complex. Together, our findings show that the open conformation of AnmK facilitates binding of both the sugar and nucleotide substrates, and that large structural rearrangements must occur upon closure of the enzyme to correctly align the substrates and residues of the enzyme for catalysis. Conformational itinerary of Pseudomonas aeruginosa 1,6-Anhydro-N-acetylmuramic acid kinase during its catalytic cycle.,Bacik JP, Tavassoli M, Patel TR, McKenna SA, Vocadlo DJ, Khajehpour M, Mark BL J Biol Chem. 2013 Dec 20. PMID:24362022 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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