Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.27 (thermolysin)
 1,894 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The primary structures of the full-length precursors of thermolysin-like proteinases (TLPs) were systemically analyzed. Structural comparison of the precursor amino-terminal regions (ATRs) removed during maturation allowed us to divide the family into two groups: peptidases with short (about 50 amino acids) and long (about 200 amino acids) ATRs. The accumulation of mutations in the ATRs of both types proved to correlate with that in the catalytic domains. No classical signal peptides were identified in the short ATRs, but they contained a conserved PPL-motif near the initiation methionine. The functional role of the short ATRs and PPL-motif is currently unclear. The C-terminal regions (CTRs) of TLP precursors, which are often removed during maturation, too, are found in about a half of precursors with long ATRs, but occur more rarely in precursors with short ATRs. CTRs in TLP precursors contain previously identified conserved domains typical for many other proteins and likely underlie the interaction with high molecular weight substrates.
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PMID:Structural organization of precursors of thermolysin-like proteinases. 1858 16

Protealysin (PLN) belongs to the M4 family of peptidases that are commonly known as thermolysin-like proteases (TLPs). All TLPs are synthesized as precursors containing N-terminal propeptides. According to the primary structure of the N-terminal propeptides, the family is divided into two distinct groups. Representatives of the first group including thermolysin and all TLPs with known three-dimensional structures have long prosequences ( approximately 200 amino acids). Enzymes of the second group, whose prototype is protealysin, have short ( approximately 50 amino acids) propeptides. Here, we present the 1.8 A crystal structure of PLN precursor (proPLN), which is the first three-dimensional structure of a TLP precursor. Whereas the structure of the catalytic domain of proPLN is similar overall to previously reported structures of mature TLPs, it has specific features, including the absence of calcium-binding sites, and different structures of the N-terminal region and substrate-binding site. PLN propeptide forms a separate domain in the precursor and likely acts as an inhibitor that blocks the substrate-binding site and fixes the "open" conformation of the active site, which is unfavorable for catalysis. Furthermore the conserved PPL motif identified in our previous studies directly interacts with the S' subsites of the active center being a critical element of the propeptide-catalytic domain interface. Comparison of the primary structures of TLPs with short propeptides suggests that the specific features revealed in the proPLN crystal structure are typical for all protealysin-like enzymes. Thus, such proteins can be considered as a separate subfamily of TLPs.
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PMID:Crystal structure of the protealysin precursor: insights into propeptide function. 1991 5