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. 2014 Dec 11;5:439. doi: 10.3389/fgene.2014.00439

Figure 2.

Figure 2

(A) Mapping alanine-scanning mutagenesis and known disease causing missense mutations in the EBP model. Alanine-scanning (Moebius et al., 1999) identified 11 residues as major determinants of EBP catalytic activity (His77, Glu81, Trp102, Tyr105, Asp109, Arg111, Tyr112, Glu123, Thr126, Asn194, and Trp197; here renumbered to the current EBP_HUMAN SwissProt entry numbering by subtracting one to the number of each position). Four (orange points) are present in exactly the same positions as are disease associated mutations (H76Y, E80K, R110Q, and W196S) and the remaining seven (W101, Y104, D108, Y111, E122, T125, and N193) (yellow points) are located in the vicinity of disease associated mutations (fewer than five residues-distant). Mapped CDPX2 disease causing missense mutations (red points), derived from Human Gene Mutation Database (HGMD) and PubMed analysis (Stenson et al., 2003), are: M1I (Steijlen et al., 2007), M1V (Hello et al., 2010), R62W (Herman et al., 2002), L66P (Whittock et al., 2003), C67R (Morice-Picard et al., 2011), W68C (Lambrecht et al., 2014), C72Y (Herman et al., 2002), I75N (Barboza-Cerda et al., 2014), H76Y (Umekoji et al., 2008), E80K (Braverman et al., 1999; Ikegawa et al., 2000; Aughton et al., 2003), W82C (Has et al., 2002; Shirahama et al., 2003), S98F (Tysoe et al., 2008), S98P (Tysoe et al., 2008), E103K (Kolb-Mäurer et al., 2008), G107R (Derry et al., 1999), R110Q (Derry et al., 1999; Hou, 2013), V119G (Non-lethal) (Cañueto et al., 2012; Bode et al., 2013), G130V (Herman et al., 2002), S133R (Braverman et al., 1999; Derry et al., 1999), R147G (Becker et al., 2001), R147H (Braverman et al., 1999; Has et al., 2000; Ikegawa et al., 2000; Shirahama et al., 2003), G157S (Herman et al., 2002), D162H (Whittock et al., 2003), L164P (Cañueto et al., 2012), Y165C (Shirahama et al., 2003), G173R (Herman et al., 2002), W196S (Herman et al., 2002), L203P (Has et al., 2002), D206Y (Ausavarat et al., 2008). L18P and W47C (Milunsky et al., 2003; Furtado et al., 2010) present a less severe phenotype called MEND (Male EBP Disorder with Neurological Defects) syndrome (Arnold et al., 2012). (B) Reaction catalyzed by EBP. Cholesterol carbon atoms C7, C8, and C9 are label.