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PDBsum entry 2vez
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References listed in PDB file
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Key reference
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Title
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Glucose-6-Phosphate as a probe for the glucosamine-6-Phosphate n-Acetyltransferase michaelis complex.
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Authors
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R.Hurtado-Guerrero,
O.Raimi,
S.Shepherd,
D.M.Van aalten.
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Ref.
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Febs Lett, 2007,
581,
5597-5600.
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PubMed id
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Abstract
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Glucosamine-6-phosphate N-acetyltransferase (GNA1) catalyses the N-acetylation
of d-glucosamine-6-phosphate (GlcN-6P), using acetyl-CoA as an acetyl donor. The
product GlcNAc-6P is an intermediate in the biosynthesis UDP-GlcNAc. GNA1 is
part of the GCN5-related acetyl transferase family (GNATs), which employ a wide
range of acceptor substrates. GNA1 has been genetically validated as an
antifungal drug target. Detailed knowledge of the Michaelis complex and
trajectory towards the transition state would facilitate rational design of
inhibitors of GNA1 and other GNAT enzymes. Using the pseudo-substrate
glucose-6-phosphate (Glc-6P) as a probe with GNA1 crystals, we have trapped the
first GNAT (pseudo-)Michaelis complex, providing direct evidence for the
nucleophilic attack of the substrate amine, and giving insight into the
protonation of the thiolate leaving group.
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