Metallo-proteases

According to their genetic relationship and their biochemical mechanism of action (3-lactamases are divided into enzymes of the serine-protease type containing an active-site serine (molecular class A, C, and D enzymes) and those of the metallo-protease type (molecular class B enzymes), which contain a complex bound zinc ion. 

Antibiotic Resistance. Figure 1 According to Bush, Jacoby and Medeiros [2] four molecular classes of (3-lactamases can be discriminated based upon biochemical and molecular features. Classes 1, 2, and 4 included serine-proteases, while metallo enzymes are included in class 3. The substrate spectrum varies between different subclasses and the corresponding genes can be part of an R-plasmid leading to a wider distribution or are encoded chromosomally in cells of specific species. 

Metallo proteases Exopeptidase group Peptidyl dipeptidase-A (ACE) Aminopeptidase-M Carboxypeptidase-A... 

Januario AH, Simone LS, Silvana M, et al. Neo-clerodane diterpenoid, a new metallo-protease snake venom inhibitor from Baccharis trimera (Asteraceae) anti-proteolytic and anti-hemorrhagic properties. Chem Biol Interact 2002 150 243-251. 

Human TNF-a is initially synthesized as a 233 amino acid polypeptide that is anchored in the plasma membrane by a single membrane-spanning sequence. This TNF pro-peptide, which itself displays biological activity, is usually proteolytically processed by a specific extracellular metallo-protease. Proteolytic cleavage occurs between residues 76 (Ala) and 77 (Val), yielding the mature (soluble) 157 amino acid TNF-a polypeptide. Mature human TNF-a appears to be devoid of a carbohydrate component, and contains a single disulfide bond. 

In A. vinelandii, C-terminal cleavage occurs in crude extracts after restoration of nickel and requires hours rather than minutes, as is the case in vivo. It does not require de novo protein synthesis and surprisingly is not redox or O2 sensitive. Also, it is not inhibited by well-established inhibitors of metallo- or serine protease families (Menon and Robson 1994). 

Based on their sequence homology, disulfide connectivity, and cysteine location within the sequence and chemistry of the reactive site. Pis can be assigned to distinct families, as classified by Laskowski and Kato. Kunitz-type, Bowman—Birk-type, Potato type I and type II, and squash inhibitors are members of these families shown in Table 3. For inhibitors not falling into these classifications more families have been proposed. Pis can also be classified by their target/mode of action. Plants have been found to express Pis that target serine proteinases, cysteine proteinases, aspartic proteinases, and metallo-proteinases. Serine and cysteine protease inhibitors are the best-studied PIs. ... 

Hydrolases that form an acyl-enzyme intermediate, such as some proteases and amidases, can be effectively used in this approach. On the other hand, this method is not applicable to metallo- and carboxyproteases. 

Protease 3D structural models matrix metallo protease-inhibitor complexes... 

Very recently, (3-lactam antibiotics have been shown to offer neuroprotection by increasing glutamate transporters expression via gene activation [15] in addition, the discoveries of new biologically active (3-lactams such as cholesterol acyl transferase inhibitors [16-18], thrombin inhibitors [19], human cytomegalovirus protease inhibitors [20], matrix-metallo protease inhibitors [21], inhibitors of human leukocyte elastase (HLE) [22, 23] and cysteine protease [24, 25], and apoptosis inductors [26, 27] have provided much needed motivation for continuous development of new (3-lactam systems. 

Peterson JT, Li H, Dillon L, Bryant JW. Evolution of metallo-protease and tissue inhibitor expression during heart failure progression in the infarcted heart, Cardiovasc Res 2000 46 307-315. 

The human plasma metallo-protease carboxypeptidase N (CPN, arginine... 

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