PMC

Ideogrammatic Representation Indicating the Overlapping HBD Regions for All Three Families on 9q34.3, the RefSeq Genes within the Common Region, the Genomic Organization of MAN1B1, and the Location within the Gene for the Three mutations

Paralogues of MAN1B1 in Humans Are Also Type 1 Mannosidases and Contain Glycosyl Hydrolase Family 47 Domains
Arg334 and Glu397 are both conserved across these paralagous sequences. Alignments were performed with CLUSTAL 2.1 multiple sequence alignment.

Pedigrees of Families MR7, MR8, and MR9 from Dera Ghazi Khan, and from MR43 from Sukkur in Pakistan, and 8600060 from Iran
Filled circles indicate affected individuals. Birth order is not assigned for generation VI in family MR43. Below the pedigrees, electropherograms from sequence analysis of MAN1B1 are shown, indicating the p.Glu397Lys, p.Trp473^∗, and p.Arg334Cys mutations, respectively. For the p.Glu397Lys and p.Arg334Cys missense mutations, the panel below the electropherograms shows CLUSTAL 2.1 multiple sequence alignment indicating conservation of the substituted amino acids in MAN1B1 orthologs across the animal kingdom in red. Nonconserved residues are shown with yellow highlighting. Photographs of the affected individuals are available on request from the corresponding author (signing of a confidentiality and nondisclosure agreement is required).

3D Protein Structure for MAN1B1 Indicating the Location of Missense Residues
The structure shows a transparent surface representation of the enzyme in gray and a stick representation of the glycan substrate (thiodisaccharide) in yellow; the mannose residues in the −1 and +1 subsites are indicated. The Ca²⁺ ion interacting with the 2′ OH and 3′ OH of the glycone residue in the −1 subsite is indicated with orange spacefill. The two amino acids that are mutated, Arg334 and Glu397, are shown in stick form in blue and are clearly located close together; they are believed to form hydrogen bonds with the substrate. The molecular display was generated with MacPymol 1.3 and the PDB file 1X9D. See for a video of the molecular structure.