Molecular Insights into the Interaction Between the SPRY Domain-Containing SOCS Box Protein SPSB2 and Peptides Based on the Binding Motif from iNOS
Eleanor WW Leung, Mark D Mulcair, Beow Keat Yap, Sandra E Nicholson, Martin J Scanlon, Raymond S Norton
Australian Journal of Chemistry | CSIRO PUBLISHING | Published : 2017
SPRY domain-containing SOCS box proteins SPSB1, 2, and 4 mediate the proteasomal degradation of inducible nitric oxide synthase (iNOS) and thereby modulate the amount of NO available for combating infectious organisms. A highly conserved Asp-Ile-Asn-Asn-Asn (DINNN) motif found at the N-terminus of iNOS binds to SPSB2 with nanomolar affinity. The design of specific and potent inhibitors of iNOS-SPSB interactions will be aided by a better understanding of the interactions of this DINNN sequence with SPSB2. Although crystal structures of SPSB complexes with DINNN peptides are available, aspects of the interaction between peptide and protein are still not fully understood. Here, our results from..View full abstract
Awarded by NHMRC
R.S.N. acknowledges fellowship support from the National Health and Medical Research Council (NHMRC) of Australia. B.K.Y. is the recipient of an Academic Staff Training Scheme Fellowship of University Sains Malaysia. This study was supported in part by NHMRC project grants 1022693 and 1099428.