M13 endopeptidases: New conserved motifs correlated with structure, and simultaneous phylogenetic occurrence of PHEX and the bony fish.
M13 endopeptidase alignments have focused mainly on mammalian sequences and on the active site region defining the catalytic sequence signatures. Aligning all available M13 from bacteria to human on a full-length basis, we have performed a sequence analysis. This enabled us to highlight the origin and function of the M13 PHEX subtype family endopeptidase (phosphate regulating gene with homologies to endopeptidases on the X chromosome). New evolutionary conserved regions in both prokaryotes and eukaryotes have been detected and eukaryotic-specific regions clearly delineated. Using the recently solved neprilysin structure, we have observed that all new motifs, except one, localize in the spatial vicinity of the previously reported catalytic signatures. Interestingly, a highly hydrophobic pocket containing three newly reported motifs is centered by the C-terminal tryptophan residue. Extensive M13 searches in complete and in progress higher eukaryotic genomes have lead to the identification of Danio rerio as the simplest organism having PHEX. Finally, the human PHEX substrate, the parathyroid hormone-related peptide, PTHrP(107-139), is absent in bony fish: this suggests the existence of further PHEX substrates common to both bony fishes and higher vertebrates.
Bianchetti
Laurent
L
Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS, INSERM, ULP), Illkirch, France. Laurent.Bianchetti@igbmc.u-strasbg.fr
Oudet
Claudine
C
Poch
Olivier
O
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006801:Humans; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000737:chemistry / Q000235:genetics; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D010802:Phylogeny; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics
D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D029961:Zebrafish Proteins; C071097:parathyroid hormone-related protein (107-139); D008666:Metalloendopeptidases; D015260:Neprilysin