TY - JOUR

T1 - Structure of the dimeric form of CTP synthase from Sulfolobus solfataricus

AU - Lauritsen, Iben H.

AU - Willemoës, Martin

AU - Jensen, Kaj Frank

AU - Johansson, Eva

AU - Harris, Pernille

PY - 2011

Y1 - 2011

N2 - CTP synthase catalyzes the last committed step in de novo pyrimidinenucleotidebiosynthesis. Active CTP synthase is a tetrameric enzyme composedof a dimer of dimers. The tetramer is favoured in the presence of the substratenucleotides ATP and UTP; when saturated with nucleotide, the tetramercompletely dominates the oligomeric state of the enzyme. Furthermore,phosphorylation has been shown to regulate the oligomeric states of theenzymes from yeast and human. The crystal structure of a dimeric form of CTPsynthase from Sulfolobus solfataricus has been determined at 2.5 A ° resolution.A comparison of the dimeric interface with the intermolecular interfaces in thetetrameric structures of Thermus thermophilus CTP synthase and Escherichiacoli CTP synthase shows that the dimeric interfaces are almost identical in thethree systems. Residues that are involved in the tetramerization of S. solfataricusCTP synthase according to a structural alignment with the E. coli enzyme allhave large thermal parameters in the dimeric form. Furthermore, they are seento undergo substantial movement upon tetramerization.

AB - CTP synthase catalyzes the last committed step in de novo pyrimidinenucleotidebiosynthesis. Active CTP synthase is a tetrameric enzyme composedof a dimer of dimers. The tetramer is favoured in the presence of the substratenucleotides ATP and UTP; when saturated with nucleotide, the tetramercompletely dominates the oligomeric state of the enzyme. Furthermore,phosphorylation has been shown to regulate the oligomeric states of theenzymes from yeast and human. The crystal structure of a dimeric form of CTPsynthase from Sulfolobus solfataricus has been determined at 2.5 A ° resolution.A comparison of the dimeric interface with the intermolecular interfaces in thetetrameric structures of Thermus thermophilus CTP synthase and Escherichiacoli CTP synthase shows that the dimeric interfaces are almost identical in thethree systems. Residues that are involved in the tetramerization of S. solfataricusCTP synthase according to a structural alignment with the E. coli enzyme allhave large thermal parameters in the dimeric form. Furthermore, they are seento undergo substantial movement upon tetramerization.

KW - Faculty of Science

KW - CTP synthase

KW - dimer-tetramer equilibrium

KW - nucleotide metabolism

U2 - 10.1107/S1744309110052334

DO - 10.1107/S1744309110052334

M3 - Journal article

C2 - 21301086

VL - 67

SP - 201

EP - 208

JO - Acta Crystallographica Section F: Structural Biology Communications

JF - Acta Crystallographica Section F: Structural Biology Communications

SN - 2053-230X

IS - 2

ER -