Fig. 8

Falcilysin mutations found in Southeast Asia. a Structure of falcilysin is shown as ribbon diagram (left panel). The N-terminal and C-terminal domains are coloured in dark green and blue, respectively. Clusters of ten Southeast Asia mutations on the outer surface of the C-terminal domain of falcilysin are shown in pink with shade representing allele frequency (right panel). K910M and S986N are Southeast Asia-exclusive mutations (allele frequencies of 1 and 0.1 %, respectively). S986R could be found predominantly in South Asia (1.4 %), Southeast Asia (0.1 %) and Africa (<0.1 %). T752S and E893D are more common in Southeast Asia (allele frequency of 2.2 and 0.3 %, respectively) but could also be found in Africa (allele frequency 0.1 and <0.1 %, respectively). Q812H, D841Y, I888N, R918C, V972L, and T976A/I are found at low frequencies (<0.1 %) in Southeast Asia and Africa. b Cross-section of falcilysin showing central cavity. The locations of catalytic zinc atom (cyan star) and Southeast Asia-specific L453M (orange star) inside the central cavity are indicated. It is the only mutation found in Southeast Asia that is located inside the central cavity. This allele has allele frequency of 0.1 %. Falcilysin active site is shown in the inset. L453M is shown as pink stick. Zinc is coordinated by His129, His133 and Glu243. Falcilysin structures were obtained from PDB ID: 3S5K and 3S5I