Journal article

Publication year: 2004

Pages: 1613-1624

Journal: Journal of Molecular Biology

Volume number: 342

Issue number: 5

ISSN: 0022-2836

eISSN: 1089-8638

DOI Link: https://doi.org/10.1016/j.jmb.2004.08.020

Publisher: Elsevier

Abstract: 
In vivo studies with the fruit-fly Drosophila melanogaster have shown that the Sniffer protein prevents age-dependent and oxidative stress-induced neurodegenerative processes. Sniffer is a NADPH-dependent carbonyl reductase belonging to the enzyme family of short-chain dehydrogenases/reductases (SDRs). The crystal structure of the homodimeric Sniffer protein from Drosophila melanogaster in complex with NADP has been determined by multiple-wavelength anomalous dispersion and refined to a resolution of 1.75 Angstrom. The observed fold represents a typical dinucleotide-binding domain as detected for other SDRs. With respect to the cofactor-binding site and the region referred to as substrate-binding loop, the Sniffer protein shows a striking similarity to the porcine carbonyl reductase (PTCR). This loop, in both Sniffer and PTCR, is substantially shortened compared to other SDRs. In most enzymes of the SDR family this loop adopts a well-defined conformation only after substrate binding and remains disordered in the absence of any bound ligands or even if only the dinucleotide cofactor is bound. In the structure of the Sniffer protein, however, the conformation of this loop is well defined, although no substrate is present. Molecular modeling studies provide an idea of how binding of substrate molecules to Sniffer could possibly occur. (C) 2004 Elsevier Ltd. All rights reserved.

Harvard Citation style: Sgraja, T., Ulschmid, J., Becker, K., Schneuwly, S., Klebe, G., Reuter, K., et al. (2004) Structural insights into the neuroprotective-acting carbonyl reductase Sniffer of Drosophila melanogaster, Journal of Molecular Biology, 342(5), pp. 1613-1624. https://doi.org/10.1016/j.jmb.2004.08.020

APA Citation style: Sgraja, T., Ulschmid, J., Becker, K., Schneuwly, S., Klebe, G., Reuter, K., & Heine, A. (2004). Structural insights into the neuroprotective-acting carbonyl reductase Sniffer of Drosophila melanogaster. Journal of Molecular Biology. 342(5), 1613-1624. https://doi.org/10.1016/j.jmb.2004.08.020