Conservation
OTCase is a highly conserved enzyme.
Sequences from bacteria to man all align readily, showing
strong conservation of residues involved in binding
carbamyl phosphate and ornithine. The severity of OTC
deficiency due to single amino acid changes (missense
mutation) in part is due to the differences in physical and
chemical properties of the amino acid substitution, but
also is due to the mutation location. Amino acids that are
important for the three dimensional fold of OTCase or
important for binding substrates or catalyzing the
enyzmatic reaction are very highly conserved. A collorary
is that regions of OTCase that are highly variable amongst
organisms also appear to be regions where mutations tend to
result in a milder form of OTC deficiency.
Shown below is a logo representation of an alignment of 566
OTCases. The numbering corresponds to the human sequence by
removing insertions relative to the human sequence. The
size of the letters indicates the degree of sequence
conservation and most of these have catalytically or
structurally important roles. The human sequence is shown
below the number track. A scalable PDF version of this
image is available here.