biostudies-literatureLewinska MNICHD NIH HHSNIEHS NIH HHSe82554https://www.ebi.ac.uk/biostudies/studies/S-EPMC3866192biostudies-literatureUnknown8(12)We investigated the housekeeping cytochrome P450 CYP51A1 encoding lanosterol 14α-demethylase from cholesterol synthesis that was so far not directly linked to human disorders. By direct sequencing of CYP51A1 in 188 women with spontaneous preterm delivery and 188 unrelated preterm infants (gestational age <37 weeks) we identified 22 variants where 10 are novel and rare. In infants there were two novel CYP51A1 variants where damaging effects of p.Tyr145Asp from the substrate recognition region, but not p.Asn193Asp, were predicted by PolyPhen2 and SIFT. This was confirmed by molecular modeling showing that Tyr145Asp substitution results in changed electrostatic potential of the CYP51 protein surface and lengthened distance to the heme which prevents hydrogen bonding. The CYP51 Tyr145Asp mutatPloS onePolymorphisms of CYP51A1 from cholesterol synthesis: associations with birth weight and maternal lipid levels and impact on CYP51 protein structure.PMC3866192HD52953P30 ES005605R01 HD052953Lewinska MRozman DMerzel FZelenko UGolic Grdadolnik SMurray JCfalsePolymorphisms of CYP51A1 from cholesterol synthesis: associations with birth weight and maternal lipid levels and impact on CYP51 protein structure.We investigated the housekeeping cytochrome P450 CYP51A1 encoding lanosterol 14α-demethylase from cholesterol synthesis that was so far not directly linked to human disorders. By direct sequencing of CYP51A1 in 188 women with spontaneous preterm delivery and 188 unrelated preterm infants (gestational age <37 weeks) we identified 22 variants where 10 are novel and rare. In infants there were two novel CYP51A1 variants where damaging effects of p.Tyr145Asp from the substrate recognition region, but not p.Asn193Asp, were predicted by PolyPhen2 and SIFT. This was confirmed by molecular modeling showing that Tyr145Asp substitution results in changed electrostatic potential of the CYP51 protein surface and lengthened distance to the heme which prevents hydrogen bonding. The CYP51 Tyr145Asp mutat2013-01-01T00:00:00Z20132026-05-02T01:50:27.854Z2019-03-26T23:17:25ZS-EPMC38661922435820410.1371/journal.pone.0082554