2VEZ

AfGNA1 crystal structure complexed with Acetyl-CoA and Glucose-6P gives new insights into catalysis

Summary for 2VEZ

• Entry DOI: 10.2210/pdb2vez/pdb
• Related: 2VXK
• Descriptor: PUTATIVE GLUCOSAMINE 6-PHOSPHATE ACETYLTRANSFERASE, ACETYL COENZYME *A, 6-O-phosphono-alpha-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: transferase, acyltransferase, glucosamine-6-phosphate n-acetyltransferase (gna1) udp-glcnac biosynthetic pathway
• Biological source: ASPERGILLUS FUMIGATUS (SARTORYA FUMIGATA)
• Total number of polymer chains: 1
• Total formula weight: 22290.79

Authors

Hurtado-Guerrero, R.,Raimi, O.,Shepherd, S.,van Aalten, D.M.F. (deposition date: 2007-10-27, release date: 2009-03-10, Last modification date: 2024-05-08)

Primary citation

Hurtado-Guerrero, R.,Raimi, O.,Shepherd, S.,Van Aalten, D.M.F.
Glucose-6-Phosphate as a Probe for the Glucosamine- 6-Phosphate N-Acetyltransferase Michaelis Complex.
FEBS Lett., 581:5597-, 2007

PubMed Abstract: 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.

PubMed: 18005663
DOI: 10.1016/J.FEBSLET.2007.10.065

Experimental method

X-RAY DIFFRACTION (1.45 Å)