Protease domain

Fig. 1 Structure of BILN 2061 and initial lead peptide DDIVPC. Activities were determined in a radiometric assay against the NS3 protease domain...

Fig. 3 A ribbon diagram of the HCV NS3/4A protease ICU1 (Yao et al, 1999). The serine protease domain is shown in cyan with the catalytic triad highlighted in yellow, and the helicase domain is...

Fig. 2.2 (A) Structure of full-length NS3 including the N-terminal protease domain (bottom) and C-terminal helicase domain (top). The NS4A peptide (purple) is covalently attached to the N-terminus of NS3 (see text). Within the protease domain the N- and C-terminal -barrels are at the right and left, respectively. The zinc atom is visible at the bottom left. [98]. (B) Surface view of the NS3 protease domain showing compound (1) bound at the relatively shallow active site (See also Fig. 2.6) [42].

L. Hong, G. Koelsch, X. Lin, S. Wu, S. Terzyan, A. K. Ghosh, X. C. Zhang, and J. Tang, Structure of the protease domain of memapsin 2-(beta-secretase) complexed with inhibitor, Science 290 150 (2000). 

The carboxy-terminal region in apolipoprotein (a) closely resembles the protease domain in plasminogen [eight amino acid substitutions, nine amino acid deletions, and one insertion in apo(a) relative to plasminogen, with 94% overall nucleotide sequence identity] (G28). The most important difference is the substitution of arginine by serine in the site responsible for proteolytic activity (position 4308) (G28). As a result, Lp(a) has no protease activity towards substrates for plasmin (J3). Salonen (SI) reported a serine-protease activity of Lp(a) towards fibronectin, a glycoprotein present in connective tissue matrices. 

The evolutionary hypothesis is that the ancestral molecule of apo(a) was a plasminogen-type protein, having five kringles, that emerged by a duplication event from a protein with one kringle and one serine protease domain about 300 million years ago (12). 

Fig. 8. Organization of the kringle IV repeats in apo(a). It has been determined that kringle IV repeats, which vary in amino acid sequence from the identically repeated kringle sequence (kringle IV types 1 and 3-10), are highly variable in the population, ranging from less than 10 to greater than 50. The numbers in brackets below the boxes refer to the kringle nomenclature described in McLean et at. (M24). Sequences corresponding to apo(a) kringle V and protease domains are indicated by stippled and solid boxes, respectively.

Trypsin-like serine proteases domains 1 and 2 Pyruvate kinase domain 2 Prealbumin Plastocyanin, azurin... 

C. Multiple, partial, and other /3 barrels Acid proteases domains 1 and 2 Alcohol dehydrogenase domain 1 Pancreatic ribonuclease... 

FI/F2/F3, triad of RING-finger-like domains F, F-box domain USP, deubiquitinase catalytic domain OTU, a particular class of cystein protease domains RVP, retroviral protease domain DBA, ubiquitin-associated domain Pkinase, protein kinase catalytic domain. 

TtrapNT A further UBA-like domain is found at the N-terminus of the TNF- and TRAF-associated protein Ttrap, as well as a number of other sequences including eight other human proteins and the yeast ORF Ylrl28w. The scope of proteins harboring the TtrapNT domain resembles that of the UBA proteins. The Cezarme -like proteins combine the TtrapNT module with an OUT-type protease domain, while other proteins also contain UIM or UBX domains. Most TtrapNT proteins have an established or predicted role in the ubiquitin pathway, making it likely that TtrapNT serves as a recognition module for ubiquitin or ubiquitin-like domains. 

Figure 7 Sequence requirements of the leader peptides of nisin, mutacin II, lacticin 481, and lacticin 3147 as determined by site-directed mutagenesis. For nisin and mutacin II, mutants that still resulted in full processing of the prepeptides are shown in green, whereas mutants that resulted in abolished lantibiotic production are shown in orange. For lacticin 481, the mutants shown in green were good substrates in vitro for either the bifunctional synthetase LctM or the protease domain of LctT, whereas the mutants in orange were poor substrates. Conserved residues in the leader peptides of subgroups of lantibiotics are indicated in blue and red as described in Figure 6.

The precursor for the class III lantibiotic SapB contains a 21-amino-acid leader peptide. Two ABC-transporters RamA and RamB, consisting of 636 and 608 amino acids, respectively, are encoded by the SapB gene cluster. RamA and RamB share 31 % sequence identity however, neither contains a serine protease or cysteine protease domain. Since no other candidate proteases are present in the gene cluster, the identity of the protease that removes the leader peptide remains elusive. 

LanT lantibiotic-specific ABC transporter (sometimes with a protease domain)... 

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