This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ye, S.
Right arrow Articles by McRee, D. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ye, S.
Right arrow Articles by McRee, D. E.

 Previous Article  |  Next Article 

Journal of Bacteriology, July 2003, p. 4144-4151, Vol. 185, No. 14
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.14.4144-4151.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Crystal Structure of Shikimate Dehydrogenase (AroE) Reveals a Unique NADPH Binding Mode

Sheng Ye, Frank von Delft, Alexei Brooun, Mark W. Knuth, Ronald V. Swanson, and Duncan E. McRee*

Syrrx Inc., San Diego, California 92121

Received 10 February 2003/ Accepted 1 May 2003

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-Å resolution and its complex with NADPH to 1.95-Å resolution. The molecule contains two domains, a catalytic domain with a novel open twisted {alpha}/ß 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.

* Corresponding author. Mailing address: Syrrx Inc., 10410 Science Center Dr., San Diego, CA 92121. Phone: (858) 731-3596. Fax: (858) 550-0526. E-mail: duncan.mcree{at}syrrx.com.

Journal of Bacteriology, July 2003, p. 4144-4151, Vol. 185, No. 14
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.14.4144-4151.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Teramoto, H., Inui, M., Yukawa, H. (2009). Regulation of Expression of Genes Involved in Quinate and Shikimate Utilization in Corynebacterium glutamicum. Appl. Environ. Microbiol. 75: 3461-3468 [Abstract] [Full Text]  
  • Singh, S., Stavrinides, J., Christendat, D., Guttman, D. S. (2008). A Phylogenomic Analysis of the Shikimate Dehydrogenases Reveals Broadscale Functional Diversification and Identifies One Functionally Distinct Subclass. Mol Biol Evol 25: 2221-2232 [Abstract] [Full Text]  
  • Lindner, H. A., Nadeau, G., Matte, A., Michel, G., Menard, R., Cygler, M. (2005). Site-directed Mutagenesis of the Active Site Region in the Quinate/Shikimate 5-Dehydrogenase YdiB of Escherichia coli. J. Biol. Chem. 280: 7162-7169 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»