Figure 6 | Scientific Reports

Figure 6

From: Mutations of the DNA repair gene PNKP in a patient with microcephaly, seizures, and developmental delay (MCSZ) presenting with a high-grade brain tumor

Figure 6

Local structures within PNKP at the sites of the amino acid changes. (A,B) Images taken from murine PNKP surrounding T322 (T323 in human PNKP). The mutation T322M appears to be minimally disruptive despite the larger size of methionine, due to the presence of a pocket that can accommodate the extended amino acid. However, potential clashes can occur with Glu 325 and Arg 292 (Glu 326 and Arg 293 in human PNKP). (C) An alignment of the FHA domain of human PNKP with the phosphopeptide binding site of XRCC4. The PNKP FHA domain is shown in orange and the XRCC4 pThr/pSer peptide is shown in red (PDB: 2W3O). A disruption in the P101/Y94 loop that causes a conformational change will affect His 100 which would affect the pThr binding interface through packing with V41 and D43. Additionally, movement in the P101/Y94 loop would affect direct binding to the pThr peptide through N97’s hydrogen bonds.

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