Fig. 7: S-nitrosylated cysteines can induce conformational changes in the proximal cysteines in different human proteins.
To account for conformational changes of the SNO and proximal cysteines, we collected coarse-grained models of the 44 human proteins identified by the SNOfinder pipeline (see Materials and Methods). A–D with subsequence all-atom reconstruction. The cartoons show the structural ensembles calculated for A thioredoxin (TXN, loop-loop class), B adenosine kinase (ADK, loop-strand class), C methionine aminopeptidase 2 (METAP2, helix-loop class), and D cullin-associated NEDD8-dissociated protein (CAND1, helix-helix class). The spheres indicate the atoms of the S-nitrosylated (SNO, orange) site and the proximal cysteine (proxy, blue). The distribution plots at the bottom of each panel show the values calculated in the coarse-grained models for i) χ1(SNO), χ1(proxy) and Sγ-Sγ distance (panel A), ii) relative solvent accessible surface area (SASA) of the SNO and proximal cysteines and Sγ-Sγ distance (panel B and C), iii) χ1(SNO), pKa of the SNO cysteine and Sγ-Sγ distance (panel D). We calculated these values using the SNOmodels pipeline (see Methods). We observe that during the simulations, the SNO site C32 of TXN (panel A) and C160 of ADK (panel B) can undergo conformational changes and explore more solvent-accessible conformations, with Sγ-Sγ distances mainly in the range of 3–7.5 Å and 5–8 Å, respectively. Furthermore, the SNO sites and proximal cysteines of TXN seem to prefer the minus state for their χ1 dihedrals. The proximal C380 of METAP2 (panel C) is on a highly dynamic loop and assumes different orientations. On the other hand, the two cysteines of CAND1 (panel D) are in α-helices that constrain their positions, with Sγ-Sγ distances larger than 7.5 Å.
