A Self-compartmentalizing Hexamer Serine Protease from Pyrococcus Horikoshii

Abstract

Background: Oligopeptidases are serine proteases cleaving only short peptides. Results: The complex channel system found within a hexameric oligopeptidase presents a rigid, double-gated model for size-based substrate selection. Conclusion:The substrate selection mechanism applied by an oligopeptidase depends on its multimerization state. Significance: Degradation of cytotoxic and misfolded proteins is aided by oligopeptidases, which are thus possible targets of cancer therapy.

Structural investigation of the cold-adapted acylaminoacyl peptidase from Sporosarcina psychrophila by atomistic simulations and biophysical methods

“…Helix α3 connects the C-terminal part of the β-propeller domain to the C-terminal domain in ApAAP and other warm-adapted AAPs (PDB entries 3AZO [43] and 4HXF [44]). This helix is lost in SpAAP and replaced by a more disordered linker.…”

EstDZ3: A New Esterolytic Enzyme Exhibiting Remarkable Thermostability

“…On the other hand, a BlastP search against PDB yielded that the closest sequence homolog of EstDZ3, which has been characterized both biochemically and structurally is the cinnamoyl esterase Lj0536 originating from Lactobacillus johnsonii (identity 29%, coverage 96%, PDB code: 3PF8) (Lai et al, 2011). The rest of the PDB hits included esterases and peptidases of bacterial and archaeal origin, such as the aforementioned Pseudomonas fluorescens aryl esterase and a Pyrococcus horikoshii acylaminoacyl peptidase (PDB code: 4HXE) (Menyhárd et al, 2013). …”

“…I-TASSER applies iterative threading assembly simulations, coupled with secondary structure enhanced Profile-Profile threading alignment and ab initio Monte Carlo simulations for unaligned regions. The top-ten threading templates selected by I-TASSER included esterases and peptidases, such as the P. horikoshii acylaminoacyl peptidase mentioned above (PDB code: 4HXE) (Menyhárd et al, 2013), the Est1E feruloyl esterase from Butyrivibrio proteoclasticus (PDB code: 2WTM) (Goldstone et al, 2010) and an acylaminoacyl peptidase from Aeropyrum pernix (PDB code: 2HU8) (Kiss et al, 2007), with sequence identities ranging from 16 to 24% and alignment coverage ranging from 84 to 96%. The presence of acylaminoacyl peptidases among the resulting threading templates is not surprising, since this type of enzymes share common sequence, structural, and functional characteristics with esterolytic enzymes.…”

Expression, purification, crystallization and preliminary X-ray diffraction analysis of acylpeptide hydrolase fromDeinococcus radiodurans

“…Biochemical characterizations of APH enzymes have been reported from thermophilic archaea, mammals and plants (Abraham & Nagle, 2013), while crystal structures have been reported from two genera of archaea (Bartlam et al, 2004;Menyhá rd et al, 2013). APH and other proteins of the S9 family share a similar monomeric structure consisting of two domains: an N-terminal sevenbladed or eight-bladed -propeller and a catalytic /-hydrolase domain.…”

“…However, the proteins have evolved different mechanisms to shield the active site to avoid the degradation of nontargeted cellular proteins. The mechanisms for substrate selectivity and access to the active sites vary across the archaeal APHs and the other S9 family enzymes (Fü lö p et al, 2000;Aertgeerts et al, 2004;Shan et al, 2005;Harmat et al, 2011;Menyhá rd et al, 2013).…”