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

in vivo (PEV)

in vitro (HMTase)

Class I – absolute conserved residues

2,7

C427Y

null

null

all HMTases

zinc coordination [37]

21

E455V

Hypo-morph

null

all HMTases

-

31

E455K

all HMTases

intramolecular charge interaction [33]

3

R469C

null

all HMTases

intramolecular charge interaction [33]

27

G491R

null

all HMTases

Adomet (substrate) binding [32]

12,23

V492E

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

null

Su(var)3-9, dim5

T in all beetles, compensated by L435G/S

9

C505Y

null

Su(var)3-9, G9a, SUVH, SETDB

L in Araneus diadematus, compensated by V585A

34

E506K

Su(var)3-9, G9a, SUVH

K in Acyrthosiphon pisum, compensation unknown (many substitutions in contact area of the residue)

320

D536N

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

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]

Krauss et al. BMC Evolutionary Biology 2006 6:18   doi:10.1186/1471-2148-6-18