Table 2 Classification of D. melanogaster Su(var)3-9 mutants, based on structure modelling and comparison with orthologous proteins.
Allele | Amino acid sub-stitution | Phenotype [6] | Conserved in | Occurrence of the substitution and compensation [50]; Function of residue | |
|---|---|---|---|---|---|
| Â | Â | in vivo (PEV) | in vitro (HMTase) | Â | Â |
Class I – absolute conserved residues | |||||
2,7 | C427Y | null | null | all HMTases | zinc coordination [37] |
21 | E455V | Hypo-morph | null | all HMTases | - |
31 | E455K | Â | Â | all HMTases | intramolecular charge interaction [33] |
3 | R469C | Â | null | all HMTases | intramolecular charge interaction [33] |
27 | G491R | Â | null | all HMTases | Adomet (substrate) binding [32] |
12,23 | V492E | Â | Â | all HMTases | intramolecular hydrophobic interaction [33] |
4,5 | G509E | null | null | all HMTases | structural residue glycine [33] |
Class II – compensable deviated residues (CPDs) | |||||
30 | A437T | Â | null | Su(var)3-9, dim5 | T in all beetles, compensated by L435G/S |
9 | C505Y | Â | null | Su(var)3-9, G9a, SUVH, SETDB | L in Araneus diadematus, compensated by V585A |
34 | E506K | Â | Â | Su(var)3-9, G9a, SUVH | K in Acyrthosiphon pisum, compensation unknown (many substitutions in contact area of the residue) |
320 | D536N | Â | Â | Su(var)3-9, dim5, G9a | N in Dictyostelium discoideum, compensated by Y537G and N538D |
32 | S562F | null | null | all HMTases | L in some G9a proteins, compensated by S599G |
13 | P571S | Hypo-morph | Hypo-morph | Su(var)3-9 (Drosophila), SUVH, dim5 | S in Mus musculus Suv39h2 and in mosquitos, compensated by C572V and H583R; A ribose hydroxyl of the methyltransferase reaction end product AdoHcy interact with the side chain carboxyl of the homologous D202 in Neurospora dim-5 [32] |
10 | D601N | null | Hypo-morph | most of all HMTases | N in mosquitos, Acyrthosiphon pisum and in some other HMTases, compensation ambiguous; involved in formation of lysine (substrate) binding channel [32] |
8 | N607Y | null | Hypo-morph | Su(var)3-9 (Drosophila) | no substitution or residue not conserved |
25 | P611L | Hypo-morph | Hypo-morph | Su(var)3-9 (Drosophila) | no substitution or residue not conserved |
319 | S616L | Â | Â | Su(var)3-9 (Drosophila) | no substitution or residue not conserved |
22 | L634F | Hypo-morph | Hypo-morph | Su(var)3-9, dim5, SETDB | F in Enallagma cyathigerum, compensated by F635M |
Class III – Uncompensated gain of function alleles | |||||
ptn | R529S | Hyper-morph | Hyper-morph | Su(var)3-9 | S in three fishes and in Acyrthosiphon pisum, local compensation is excluded; the side chain of the homologous L317 in Neurospora dim-5 is involved in HMTase activity [32] |