TY - JOUR
T1 - Threonine aldolase and alanine racemase
T2 - Novel examples of convergent evolution in the superfamily of vitamin B6-dependent enzymes
AU - Paiardini, Alessandro
AU - Contestabile, Roberto
AU - D'Aguanno, Simona
AU - Pascarella, Stefano
AU - Bossa, Francesco
PY - 2003/4/11
Y1 - 2003/4/11
N2 - Vitamin B6-dependent enzymes may be grouped into five evolutionarily unrelated families, each having a different fold. Within fold type I enzymes, L-threonine aldolase (L-TA) and fungal alanine racemase (AlaRac) belong to a subgroup of structurally and mechanistically closely related proteins, which specialised during evolution to perform different functions. In a previous study, a comparison of the catalytic properties and active site structures of these enzymes suggested that they have a catalytic apparatus with the same basic features. Recently, recombinant D-threonine aldolases (D-TAs) from two bacterial organisms have been characterised, their predicted amino acid sequences showing no significant similarities to any of the known B 6 enzymes. In the present work, a comparative structural analysis suggests that D-TA has an α/β barrel fold and therefore is a fold type III B6 enzyme, as eukaryotic ornithine decarboxylase (ODC) and bacterial AlaRac. The presence of both TA and AlaRac in two distinct evolutionary unrelated families represents a novel and interesting example of convergent evolution. The independent emergence of the same catalytic properties in families characterised by completely different folds may have not been determined by chance, but by the similar structural features required to catalyse pyridoxal phosphate-dependent aldolase and racemase reactions.
AB - Vitamin B6-dependent enzymes may be grouped into five evolutionarily unrelated families, each having a different fold. Within fold type I enzymes, L-threonine aldolase (L-TA) and fungal alanine racemase (AlaRac) belong to a subgroup of structurally and mechanistically closely related proteins, which specialised during evolution to perform different functions. In a previous study, a comparison of the catalytic properties and active site structures of these enzymes suggested that they have a catalytic apparatus with the same basic features. Recently, recombinant D-threonine aldolases (D-TAs) from two bacterial organisms have been characterised, their predicted amino acid sequences showing no significant similarities to any of the known B 6 enzymes. In the present work, a comparative structural analysis suggests that D-TA has an α/β barrel fold and therefore is a fold type III B6 enzyme, as eukaryotic ornithine decarboxylase (ODC) and bacterial AlaRac. The presence of both TA and AlaRac in two distinct evolutionary unrelated families represents a novel and interesting example of convergent evolution. The independent emergence of the same catalytic properties in families characterised by completely different folds may have not been determined by chance, but by the similar structural features required to catalyse pyridoxal phosphate-dependent aldolase and racemase reactions.
KW - Alanine racemase
KW - Catalytic mechanism
KW - Convergent evolution
KW - Homology modelling
KW - Pyridoxal phosphate
KW - Threonine aldolase
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U2 - 10.1016/S1570-9639(03)00050-5
DO - 10.1016/S1570-9639(03)00050-5
M3 - Article
C2 - 12686135
AN - SCOPUS:0037974655
VL - 1647
SP - 214
EP - 219
JO - Biochimica et Biophysica Acta - Proteins and Proteomics
JF - Biochimica et Biophysica Acta - Proteins and Proteomics
SN - 1570-9639
IS - 1-2
ER -