Molecular modeling of sla Hp reveals retention of core catalytic domains. (A) Ribbon diagram of mouse hephaestin. A top view along the pseudo–3-fold axis highlighting the sla deletion in black with the missing T1 Cu in domain 4. The figures were generated by using a modified version of Molscript31 and subsequently rendered in Raster3D version 2.0.32,33 (B) An alignment of Cp and Hp sequences showing the residues coordinating the mononuclear Cu in domain 2. The canonical blue Cu environment for mononuclear type 1 Cu is preserved in Hp and interestingly in zebrafish Cp but not in higher mammalian Cps. Accession numbers for the sequences are U49430, mouse Cp (mCp); L33869, rat Cp (rCp); M13699, human Cp (hCp); BC048037, zebrafish Cp (zCp); AF082567, mouse Hp; AF246120, rat Hp; and AJ296162, human Hp (hHp). *Indicates sequence identity in all proteins, whereas: indicates conservative substitutions. (C) The putative structural arrangement of Cu-binding sites in mHp. The additional methionine (mHp: 357) in domain 2 mononuclear type 1 site of Hp replaces the nonpolar leucine of hCp (L348) at the homologous position. The figure is based on the Cu centers in human Cp.11 The distances between the different Cu atoms are indicated. The brackets indicate the T1 Cu atoms in domains 2 and 4 that are unavailable for participation in the redox reactions in Cp and sla Hp, respectively.