2G09

X-ray structure of mouse pyrimidine 5'-nucleotidase type 1, product complex

Summary for 2G09

• Entry DOI: 10.2210/pdb2g09/pdb
• Related: 2BDU 2G06 2G07 2G08 2G0A
• Descriptor: Cytosolic 5'-nucleotidase III, MAGNESIUM ION, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: uniprot q9d020, umph-1, cytosolic 5'-nucleotidase iii, pyrimidine 5'-nucleotidase 1, p5n-1, nt5c3 protein, aah38029, bc038029, mm.158936, lead poisoning, structural genomics functional follow-up study, protein structure initiative, psi, center for eukaryotic structural genomics, cesg, hydrolase
• Biological source: Mus musculus (house mouse)
• Cellular location: Cytoplasm : Q9D020
• Total number of polymer chains: 2
• Total formula weight: 69171.14

Authors

Bitto, E.,Bingman, C.A.,Wesenberg, G.E.,Phillips Jr., G.N.,Center for Eukaryotic Structural Genomics (CESG) (deposition date: 2006-02-11, release date: 2006-04-04, Last modification date: 2023-11-15)

Primary citation

Bitto, E.,Bingman, C.A.,Wesenberg, G.E.,McCoy, J.G.,Phillips, G.N.
Structure of pyrimidine 5'-nucleotidase type 1. Insight into mechanism of action and inhibition during lead poisoning.
J.Biol.Chem., 281:20521-20529, 2006

PubMed Abstract: Eukaryotic pyrimidine 5'-nucleotidase type 1 (P5N-1) catalyzes dephosphorylation of pyrimidine 5'-mononucleotides. Deficiency of P5N-1 activity in red blood cells results in nonspherocytic hemolytic anemia. The enzyme deficiency is either familial or can be acquired through lead poisoning. We present the crystal structure of mouse P5N-1 refined to 2.35 A resolution. The mouse P5N-1 has a 92% sequence identity to its human counterpart. The structure revealed that P5N-1 adopts a fold similar to enzymes of the haloacid dehydrogenase superfamily. The active site of this enzyme is structurally highly similar to those of phosphoserine phosphatases. We propose a catalytic mechanism for P5N-1 that is also similar to that of phosphoserine phosphatases and provide experimental evidence for the mechanism in the form of structures of several reaction cycle states, including: 1) P5N-1 with bound Mg(II) at 2.25 A, 2) phosphoenzyme intermediate analog at 2.30 A, 3) product-transition complex analog at 2.35 A, and 4) product complex at 2.1A resolution with phosphate bound in the active site. Furthermore the structure of Pb(II)-inhibited P5N-1 (at 2.35 A) revealed that Pb(II) binds within the active site in a way that compromises function of the cationic cavity, which is required for the recognition and binding of the phosphate group of nucleotides.

PubMed: 16672222
DOI: 10.1074/jbc.M602000200

Experimental method

X-RAY DIFFRACTION (2.1 Å)