4mum

Crystal structure of mitochondrial 5'(3')-deoxy ribonucleotidase alternative spliced variant

spinqualitylabelsall models 4mum, resolution 1.27Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4mum is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.271Å Ligands: CL, GOL, MG, PEG, PG4, PO4, TRS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NT5M_HUMAN Dephosphorylates specifically the 5' and 2'(3')-phosphates of uracil and thymine deoxyribonucleotides, and so protects mitochondrial DNA replication from excess dTTP. Has only marginal activity towards dIMP and dGMP. Publication Abstract from PubMed Abstract Human mitochondrial 5'(3')-deoxyribonucleotidase (mdN) catalyzes dephosphorylation of nucleoside monophosphates, and thus helps maintain homeostasis of deoxynucleosides required for mitochondrial DNA synthesis. Mature mdN is a 23-kDa dimeric protein with highest expression levels in the heart, brain and skeletal muscle. We have identified an alternative splice variant of the mdN gene containing an 18-nucleotide insertion encoding 6 amino acids (GKWPAT) at the 3'-end of the penultimate exon 4. We recombinantly expressed this enzyme variant and characterized its biochemical and kinetic properties as well as its three-dimensional structure. Our high-resolution (1.27 A) crystal structure revealed that the insertion forms a loop located in the vicinity of the active site pocket and affects enzyme kinetic parameters as well as protein thermal stability. Kinetic and structural characterization of an alternatively spliced variant of human mitochondrial 5'(3')-deoxyribonucleotidase.,Pachl P, Fabry M, Veverka V, Brynda J, Rezacova P J Enzyme Inhib Med Chem. 2014 Feb 10. PMID:24506201 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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