Datasets, processing and refinement details for Mtb-AnPRT: inhibitor structures with various space groups

There are twenty-five published structures of Mycobacterium tuberculosis anthranilate phosphoribosyltransferase (Mtb-AnPRT) that use the same crystallization protocol. The structures include protein complexed with natural and alternative substrates, protein:inhibitor complexes, and variants with mutations of substrate-binding residues. Amongst these are varying space groups (i.e. P2 1 , C2, P2 1 2 1 2, P2 1 2 1 2 1 ). This article outlines experimental details for 3 additional Mtb-AnPRT:inhibitor structures. For one protein:inhibitor complex, two datasets are presented – one generated by crystallization of protein in the presence of the inhibitor and another where a protein crystal was soaked with the inhibitor. Automatic and manual processing of these datasets indicated the same space group for both datasets and thus indicate that the space group differences between structures of Mtb-AnPRT:ligand complexes are not related to the method used to introduce the ligand

Datasets, processing and refinement details for Mtb-AnPRT: inhibitor structures with various space groups

There are twenty-five published structures of Mycobacterium tuberculosis anthranilate phosphoribosyltransferase (Mtb-AnPRT) that use the same crystallization protocol. The structures include protein complexed with natural and alternative substrates, protein:inhibitor complexes, and variants with mutations of substrate-binding residues. Amongst these are varying space groups (i.e. P21, C2, P21212, P212121). This article outlines experimental details for 3 additional Mtb-AnPRT:inhibitor structures. For one protein:inhibitor complex, two datasets are presented â one generated by crystallization of protein in the presence of the inhibitor and another where a protein crystal was soaked with the inhibitor. Automatic and manual processing of these datasets indicated the same space group for both datasets and thus indicate that the space group differences between structures of Mtb-AnPRT:ligand complexes are not related to the method used to introduce the ligand. Keywords: Crystallography, Macromolecules, X-ray diffraction, Ligand binding, Structure-based inhibitor desig

Natural history and cell of origin of TCF3-ZNF384 and PTPN11 mutations in monozygotic twins with concordant BCP-ALL

To the editor: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common childhood cancer and is molecularly heterogeneous. Identical twins with concordant BCP-ALL have provided a unique and tractable model to delineate the natural history and clonal evolution of the disease. Such studies have led to the 2-hit model for pediatric BCP-ALL, elucidated by Greaves, which provides unambiguous evidence that an initiating alteration, often occurring in utero, generates a preleukemic clone, which eventually gives rise to an overt leukemia upon acquisition of secondary cooperating mutations. Importantly, genome-wide sequencing has revealed a strikingly silent mutational landscape in childhood BCP-ALL, further indicative of a developmental cancer of prenatal origin, with a short window of time to accumulate molecular alterations.Peer reviewe