4-Amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P) synthase catalyzes a complex rearrangement of 5-aminoimidazole ribonucleotide (AIR) to form HMP-P, the pyrimidine moiety of thiamine phosphate. We determined the three-dimensional structures of HMP-P synthase and its complexes with the product HMP-P and a substrate analog imidazole ribotide. The structure of HMP-P synthase reveals a homodimer in which each protomer comprises three domains: an N-terminal domain with a novel fold, a central (betaalpha)(8) barrel and a disordered C-terminal domain that contains a conserved CX(2)CX(4)C motif, which is suggestive of a [4Fe-4S] cluster. Biochemical studies have confirmed that HMP-P synthase is iron sulfur cluster-dependent, that it is a new member of the radical SAM superfamily and that HMP-P and 5'-deoxyadenosine are products of the reaction. Mössbauer and EPR spectroscopy confirm the presence of one [4Fe-4S] cluster. Structural comparisons reveal that HMP-P synthase is homologous to a group of adenosylcobalamin radical enzymes. This similarity supports an evolutionary relationship between these two superfamilies.
4-Amino-5-hydroxymethyl-2-methylpyrimidine phosphate (n>an class="Chemical">HMP-P) synthase catalyzes a complex rearrangement of 5-aminoimidazole ribonucleotide (AIR) to form HMP-P, the pyrimidine moiety of thiamine phosphate. We determined the three-dimensional structures of HMP-P synthase and its complexes with the product HMP-P and a substrate analog imidazole ribotide. The structure of HMP-P synthase reveals a homodimer in which each protomer comprises three domains: an N-terminal domain with a novel fold, a central (betaalpha)(8) barrel and a disorderedC-terminal domain that contains a conserved CX(2)CX(4)C motif, which is suggestive of a [4Fe-4S] cluster. Biochemical studies have confirmed that HMP-P synthase is iron sulfurcluster-dependent, that it is a new member of the radical SAM superfamily and that HMP-P and 5'-deoxyadenosine are products of the reaction. Mössbauer and EPR spectroscopy confirm the presence of one [4Fe-4S] cluster. Structural comparisons reveal that HMP-P synthase is homologous to a group of adenosylcobalamin radical enzymes. This similarity supports an evolutionary relationship between these two superfamilies.
Authors: A T Brünger; P D Adams; G M Clore; W L DeLano; P Gros; R W Grosse-Kunstleve; J S Jiang; J Kuszewski; M Nilges; N S Pannu; R J Read; L M Rice; T Simonson; G L Warren Journal: Acta Crystallogr D Biol Crystallogr Date: 1998-09-01
Authors: T P Begley; D M Downs; S E Ealick; F W McLafferty; A P Van Loon; S Taylor; N Campobasso; H J Chiu; C Kinsland; J J Reddick; J Xi Journal: Arch Microbiol Date: 1999-04 Impact factor: 2.552
Authors: F Mancia; N H Keep; A Nakagawa; P F Leadlay; S McSweeney; B Rasmussen; P Bösecke; O Diat; P R Evans Journal: Structure Date: 1996-03-15 Impact factor: 5.006
Authors: Shridhar Bale; Kanagalaghatta R Rajashankar; Kay Perry; Tadhg P Begley; Steven E Ealick Journal: Biochemistry Date: 2010-10-19 Impact factor: 3.162
Authors: Shawn E McGlynn; Eric S Boyd; Eric M Shepard; Rachel K Lange; Robin Gerlach; Joan B Broderick; John W Peters Journal: J Bacteriol Date: 2009-11-06 Impact factor: 3.490