Table 1

Classes of SAM binding proteins

Reaction summary

Trivial name, EC number

Sequence families and spatial folds (summary)

Evolutionary roots and status in LUCA


Methyl transfer

SAM-dependent methyltransferase, EC:2.1.1.-

Five classes: I, Rossmann fold; II, reactivation domain of methionine synthase; III, "corrinoid-like" MTases; IV, SPOUT domain; V, SET domain. Classes I-IV are α/β folds, class V is a β-clip. The Rossmann-fold MTases are the largest class of SAM-dependent enzymes. The folds of Classes II and III are unique. Trm10 and TrmH families of RNA MTases appear to be the modified versions, of, respectively, class IV fold [47], [49] and class I fold fused to PP-superfamily ATPase (this study). GTP MTase of Sindbis-like viruses may belong to α/β class, but specific fold prediction is unavailable

Several distinct Rossmann-fold methyl transferases in LUCA.

Methylene transfer

Cyclopropane fatty acid synthase, EC:2.1.1.79

Rossmann-fold methyltransferase family

Derived from an ancient enzyme; not in LUCA

Aminoalkyl transfer 1

Nicotianamine synthase, EC:2.5.1.43

Rossmann-fold methyltransferase family with permuted order of sequence motifs

Derived from an ancient enzyme; not in LUCA

ACC synthase, EC:4.4.1.14

PLP-dependent aminotransferase fold; the SAM-binding domain is derived from generic substrate-binding cleft

Derived from an ancient enzyme; not in LUCA

Acyl-homoserine lactone synthase, EC:6.1.-

GNAT-type acetyltransferase fold; the SAM-binding domain is derived from generic substrate-binding cleft

Derived from an ancient enzyme; not in LUCA

Aminopropyl transfer

Spermidine synthase, EC:2.5.1.16

Rossmann-fold methyltransferase family, but the substrate is decarboxy-SAM

Probably in LUCA

Ribosyl transfer

tRNA-ribosyl transferase-isomerase, EC:5.-

QueA family; smaller β-barrel N-terminal domain and a larger C-terminal domain with α/β fold, distantly related to a TIM-barrel

Bacterial invention; not in LUCA

5'deoxyadenosyl transfer

5'-fluoro-5'-deoxy-adenosine synthase, EC:2.5.1.63

Two-domains; larger N-terminal domain has distant similarity to Rossmann-fold methyltransferases, smaller C-terminal domain is a β-barrel

Bacterial invention; not in LUCA

5'deoxyadenosyl radical synthesis

SAM radical enzymes

TIM-like α/β barrel with additional inserted elements. May have distant sequence similarity to TIM barrel of corrinoid methyltransferase (see text)

Probably in LUCA

SAM decarboxylation

SAM decarboxylase, EC:4.1.1.50

α/β/β/α sandwich in eukaryotes, apparently produced by duplication of a half-unit; stand-alone half-units exist in many bacteria and archaea

Probably in LUCA

De novo SAM synthesis

Methionine adenosyl transferase, EC:2.5.1.6

Unique fold: repeat of 3 β-α-β-β-α-β units

Probably in LUCA

Regulatory binding of SAM

Methionine repressor

All-α SAM-binding domain is derived from generic small molecule-binding domain

Bacterial innovation

CBS domain

Mostly-β SAM-binding domain is derived from generic small molecule-binding domain

Not in LUCA

Transcription factor mtTFB

Rossmann-fold methyltransferase family member that has lost catalytic activity


1 An additional reaction in this class is synthesis of acp3U, a modified base in some tRNAs and rRNAs. This amino alkyl transfer requires SAM, but responsible protein has not been identified.

Kozbial and Mushegian BMC Structural Biology 2005 5:19   doi:10.1186/1472-6807-5-19

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