Structural relationship between lipases and peptidases of the prolyl oligopeptidase family

@article{Polgar1992StructuralRB,
  title={Structural relationship between lipases and peptidases of the prolyl oligopeptidase family},
  author={László Polgár},
  journal={FEBS Letters},
  year={1992},
  volume={311}
}
In prolyl oligopeptidase and its homologues, which constitute a new serine protease family, the order of the catalytic Ser and His residues in the amino acid sequence is the reverse of what is found in the trypsin and subtilisin families. The exact position of the third member of the catalytic triad, an Asp residue, has not yet been identified in the new family. Recent determination of the three‐dimensional structures of pancreatic and microbial lipases has shown that the order of their… Expand
The prolyl oligopeptidase family
  • L. Polgár
  • Chemistry, Medicine
  • Cellular and Molecular Life Sciences CMLS
  • 2002
TLDR
The recent crystal structure determination of prolyl oligopeptidase has shown that the enzyme contains a peptidase domain with an α/β hydrolase fold, and its catalytic triad is covered by the central tunnel of an unusual seven-bladed β-propeller, excluding large, structured peptides from the active site. Expand
Evolutionary relationships of the prolyl oligopeptidase family enzymes.
TLDR
The phylogenetic trees indicate that the four POP family enzymes were present in the last common ancestor of all life forms and that the beta-propeller domain has been part of the family for billions of years. Expand
Review The prolyl oligopeptidase family
TLDR
The recent crystal structure deter- mination of prolyl oligopeptidase has shown that the enzyme contains a peptidase domain with an a/b hydrolase fold, and its catalytic triad is covered by the central tunnel of an unusual seven-bladed b-propeller. Expand
Structures of Prolyl Oligopeptidase Substrate/Inhibitor Complexes
Structure determination of the inactive S554A variant of prolyl oligopeptidase complexed with an octapeptide has shown that substrate binding is restricted to the P4-P2′ region. In addition, it hasExpand
Mycobacterium tuberculosis puromycin hydrolase displays a prolyl oligopeptidase fold and an acyl aminopeptidase activity
TLDR
The crystal structure of a M. tuberculosis puromycin hydrolase peptidase has been determined at 3 Angstrom resolution, revealing a conserved prolyl oligopeptidase fold defined by α/β‐hydrolase and β‐propeller domains with two distinctive loops that occlude access of large substrates to the active site. Expand
Understanding the cellular role of prolyl oligopeptidase
TLDR
It has been determined that DpoA is highly similar to the mammalian enzyme and it has been demonstrated that while some variation was observed at the sequence level there is clear homology around the active site and the catalytic triad is conserved. Expand
Prolyl Oligopeptidase An Unusual β-Propeller Domain Regulates Proteolysis
TLDR
A resolution crystal structure of prolyl oligopeptidase, a large cytosolic enzyme that belongs to a new class of serine peptidases, is presented, which may facilitate drug design to treat memory disorders. Expand
Lipases and alpha/beta hydrolase fold.
TLDR
This chapter reviews the features of the α/β hydrolase fold and the resources used to identify similarities in the rapidly growing number of enzymes and proteins that share this fold. Expand
His507 of acylaminoacyl peptidase stabilizes the active site conformation, not the catalytic intermediate
Acylaminoacyl peptidase is a member of the prolyl oligopeptidase family. Amino acid sequence alignment suggests that the stabilization of the tetrahedral intermediate should be mediated by His507Expand
Concerted structural changes in the peptidase and the propeller domains of prolyl oligopeptidase are required for substrate binding.
TLDR
Engineering disulfide bridges to the expected oscillating structures prevented such movements, which destroyed the catalytic activity and precluded substrate binding, indicating that concerted movements of the propeller and the peptidase domains are essential for the enzyme action. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 25 REFERENCES
Oligopeptidases, and the emergence of the prolyl oligopeptidase family.
TLDR
Study of the primary structure of prolyl oligopeptidase has recently shown that it is a member of a new family of serine-type peptidases most of which are exopeptIDases, which apparently perform important, specialized biological functions that include the modification or destruction of peptide messenger molecules. Expand
Structure of human pancreatic lipase
TLDR
The structural results are evidence that Ser 152 is the nucleophilic residue essential for catalysis, located in the larger N-terminal domain at the C- terminal edge of a doubly wound parallel β-sheet and part of an Asp-His-Ser triad, which is chemically analogous to, but structurally different from, that in the serine proteases. Expand
Ser-His-Glu triad forms the catalytic site of the lipase from Geotrichum candidum
TLDR
The three-dimensional structure of a lipase from G. candidum is reported at 2.2 Å resolution, and the catalytic triad of GCL is Ser-His-Glu, with glutamic acid replacing the usual aspartate. Expand
Prolyl endopeptidase catalysis. A physical rather than a chemical step is rate-limiting.
  • L. Polgár
  • Chemistry, Medicine
  • The Biochemical journal
  • 1992
TLDR
This result, combined with kinetic isotope studies, offers strong evidence that a physical step, presumably a conformational change associated with substrate binding, is the rate-determining step in the prolyl endopeptidase catalysis. Expand
Inactivation of prolyl endopeptidase by a peptidylchloromethane. Kinetics of inactivation and identification of sites of modification.
TLDR
The substrate was shown to compete for the formation of the initial complex, indicating that binding at the active site was a prerequisite for inactivation of prolyl endopeptidase. Expand
Acylpeptide hydrolase: inhibitors and some active site residues of the human enzyme.
TLDR
Ebelactone A, an inhibitor of the formyl aminopeptidase, the bacterial counterpart of eukaryotic acylpeptide hydrolase, was found to be an effective inhibitor of this enzyme. Expand
pH-dependent mechanism in the catalysis of prolyl endopeptidase from pig muscle.
  • L. Polgár
  • Chemistry, Medicine
  • European journal of biochemistry
  • 1991
TLDR
It is concluded that a general base/acid-catalyzed acylated step is rate-limiting in the lower pH range, and an isotopically silent step, probably a conformational change preceding acylation, dominates the reaction in the physiological pH range. Expand
cDNA cloning of porcine brain prolyl endopeptidase and identification of the active-site seryl residue.
TLDR
The deduced amino acid sequence of prolyl endopeptidase showed no sequence homology with other known serine proteases, and this difference and the lack of overall homological with the known families ofserine protease suggest that prolyL endopePTidase represents a new type of serine protector. Expand
Identification of the active site residues in dipeptidyl peptidase IV by affinity labeling and site-directed mutagenesis.
TLDR
Results indicate that the sequence Gly-X-Ser-(Tyr)-Gly is essential for the expression of the DPPIV activity. Expand
Structure of wheat serine carboxypeptidase II at 3.5-A resolution. A new class of serine proteinase.
TLDR
The structure of serine carboxypeptidase II from wheat bran has been determined to 3.5-A resolution by multiple isomorphous replacement, solvent flattening, and crystallographic refinement, suggesting that this is a third example of convergent evolution to a common enzymatic mechanism. Expand
...
1
2
3
...