The crystal structure of shikimate dehydrogenase (AroE) reveals a unique NADPH binding mode.

Journal article

Shikimate dehydrogenase catalyzes the NADPH-dependent reversible reduction of 3-dehydroshikimate to shikimate. We report the first X-ray structure of shikimate dehydrogenase from Haemophilus influenzae to 2.4-A resolution and its complex with NADPH to 1.95-A resolution. The molecule contains two domains, a catalytic domain with a novel open twisted alpha/beta motif and an NADPH binding domain with a typical Rossmann fold. The enzyme contains a unique glycine-rich P-loop with a conserved sequence motif, GAGGXX, that results in NADPH adopting a nonstandard binding mode with the nicotinamide and ribose moieties disordered in the binary complex. A deep pocket with a narrow entrance between the two domains, containing strictly conserved residues primarily contributed by the catalytic domain, is identified as a potential 3-dehydroshikimate binding pocket. The flexibility of the nicotinamide mononucleotide portion of NADPH may be necessary for the substrate 3-dehydroshikimate to enter the pocket and for the release of the product shikimate.

Authors: Ye, S; von Delft, F; Brooun, A; Knuth, M; Swanson, R

• Publication status: Published
• Journal: Journal of bacteriology
• Volume: 185
• Issue: 14
• Pages: 4144-4151
• Publication date: 2003-07-01
• DOI: 10.1128/jb.185.14.4144-4151.2003
• EISSN: 1098-5530
• ISSN: 0021-9193
• Language: English
• Keywords: Molecular Sequence Data; Protein Conformation; NADP; Humans; Models, Molecular; Shikimic Acid; Alcohol Oxidoreductases; Crystallography, X-Ray; Protein Structure, Tertiary; Binding Sites; Haemophilus influenzae; Amino Acid Sequence; Sequence Alignment; Catalytic Domain