Signal Peptidases

AC A8 A08.001 Signal peptidase II Drug target for Mycobacterium tuberculosis infection... 

SF S26 S26.001 Signal peptidase I Potential drug target for antibacterial agents... 

The infectious cycle of a (+)-strand RNA virus such as the hepatitis C virus differs by the fate of the viral RNA genome in the infected cell. Upon entry into the cell, the HCV genome is used as a messenger RNA to drive the synthesis of a large polyprotein precursor of about 3,000 residues [2]. The structural proteins are excised from the precursor by host cell signal peptidase. 

Usually cleaved off at the carboxyl terminal end of an Ala residue by signal peptidase... 

Ribosomes remain attached to the ER during synthesis of signal peptide-containing proteins but are released and dissociated into their two types of subunits when the process is completed. The signal peptide is hydrolyzed by signal peptidase, located on the luminal side of the ER membrane (Figure 46-4), and then is apparently rapidly degraded by proteases. 

The substrate specificity of the type I signal peptidases is known as the ( — 3, —1) rule observed at the c-region of signal peptides (von Heijne, 1984 Jain et al., 1994), where the residues at positions —3 and -1 from the cleavage site (i.e., cleavage occurs at the peptide bond between —1/ + 1 positions) are usually small (and neutral) residues, such as alanine. Recently, the x-ray crystallographic structure of the signal... 

Folz,R., and Gordon, J. (1987). Computers-assisted predictions of signal peptidase processing sites. Biochem. Biophys. Res. Comm. 146, 870-877. 

Paetzel, M., Dalbey, R., and Strynadka, N. (1998). Crystal structure of a bacterial signal peptidase in complex with a /3-lactam inhibitor. Nature 396, 186-190. 

SF 4 Families of endopeptidases (including signal peptidases in family S26) Ser, Lys (His) Single /3-barrel... 

The site of synthesis of numerous proteins is remote from their site of function. During transfer from one site to the other, proteins must, therefore, cross cellular membranes [43] [44], Proteins are usually synthesized as precursors containing an amino terminal extension, called the signal (leader) peptide, the sequence of which contains the necessary information to guide the protein to and across a specific membrane. After transmembrane transport (called translocation), the signal peptide is cleaved off by specific signal peptidases, which are found in the rough endoplasmic reticulum, and the... 

The hydrophobic signal sequence is removed by signal peptidase in the RER to form pro-a chains. 

AM-001, and mannanase B properties are similar to those of P-mannanase M-III. Furthermore, the Ouchterlony double diffusion test showed that these five enzymes gave fused precipitation lines. However, N-terminal amino acid sequences of the five mannanases determined by an automatic amino acid sequencer revealed that the N-terminal amino acid sequence from amino acid 1 (Asn) to 9 (Gin) of the Bacillus sp. AM-001 enzymes coincides with those from amino acid 4 (Asn) to 12 (Asn) of the R coll JMlOl (pMAH3) enzymes as shown in Fig. 4. This may reflect differences in the specificities of the signal peptidases of the two bacteria. 

This enzyme [EC 3.4.21.89], also known as signal peptidase I and phage-procoat-leader peptidase, catalyzes the hydrolysis of N-terminal leader sequences from secreted and periplasmic protein precursors. It acts on a single bond Ala-Ala in the m-13 phage procoat protein and creates the signal (leader) peptide and coat protein. It is a member of the peptidase family S26 but is unaffected by inhibitors of most serine peptidases. 

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