9.B.50 The Outer Membrane Beta-barrel Endoprotease, Omptin (Omptin) Family

The Omptin family is a large family of outer membrane proteases/adhesins, found and studied primarily in enterobacteria (Kukkonen and Korhonen, 2004. They play important roles in the degradation of denatured periplasmic proteins (in E. coli), and funtion in pathogenesis (in Shigella, Escherichia, Yersinia and Salmonella species). In Yersinia pestis, the Pla protein is a plasminogen activator. It both activates plasminogen and inactivates α2-antiplasmin (Suomalainen et al., 2007). It also degrades complement components. In E. coli, omptins, OmpT and OmpP, have been shown to cleave and inactivate cationic antimicrobial peptides (Kukkonen and Korhonen, 2004), and peptide conformation is a specificity determinant (Brannon et al. 2015). OmpT of E. coli cleaves peptide bonds between two basic amino acids using a histidyl residue and an aspartyl residue at the active site of the protease, and surprisingly, this enzyme is functional in high concentrations of urea (Stathopoulos, 1998; Hritonenko and Stathopoulos, 2007).

The omptins Pla (Yersinia) and PgtE (Salmonella) attack innate immunity by affecting the plasminogen/plasmin, complement, coagulation, fibrinolysis, and matrix metalloproteinase systems. They also function by enhancing bacterial adhesiveness and invasiveness (Haiko et al., 2009; Yun and Morrissey, 2009; Korhonen et al., 2013). Although the mechanistic details and functions of Pla and PgtE differ, the outcome is the same: enhanced spread and multiplication of Y. pestis and S. enterica in the host. Maximal activity requires association with lipopolysaccharide (Hritonenko and Stathopoulos, 2007).  Aprotinin is an omptin protease inhibitor (Brannon et al. 2015).



This family belongs to the Outer Membrane Pore-forming Protein I (OMPP-I) Superfamily .

 

References:

Brannon, J.R., D.L. Burk, J.M. Leclerc, J.L. Thomassin, A. Portt, A.M. Berghuis, S. Gruenheid, and H. Le Moual. (2015). Inhibition of outer membrane proteases of the omptin family by aprotinin. Infect. Immun. 83: 2300-2311.

Brannon, J.R., J.L. Thomassin, S. Gruenheid, and H. Le Moual. (2015). Antimicrobial Peptide Conformation as a Structural Determinant of Omptin Protease Specificity. J. Bacteriol. 197: 3583-3591.

Haiko, J., M. Suomalainen, T. Ojala, K. Lähteenmäki, and T.K. Korhonen. (2009). Invited review: Breaking barriers--attack on innate immune defences by omptin surface proteases of enterobacterial pathogens. Innate Immun 15: 67-80.

Hritonenko, V. and C. Stathopoulos. (2007). Omptin proteins: an expanding family of outer membrane proteases in Gram-negative Enterobacteriaceae. Mol. Membr. Biol. 24: 395-406.

Korhonen, T.K., J. Haiko, L. Laakkonen, H.M. Järvinen, and B. Westerlund-Wikström. (2013). Fibrinolytic and coagulative activities of Yersinia pestis. Front Cell Infect Microbiol 3: 35.

Kukkonen, M. and T.K. Korhonen. (2004). The omptin family of enterobacterial surface proteases/adhesins: from housekeeping in Escherichia coli to systemic spread of Yersinia pestis. Int. J. Med. Microbiol. 294: 7-14.

Stathopoulos, C. (1998). Structural features, physiological roles, and biotechnological applications of the membrane proteases of the OmpT bacterial endopeptidase family: a micro-review. Membr Cell Biol 12: 1-8.

Suomalainen, M., J. Haiko, P. Ramu, L. Lobo, M. Kukkonen, B. Westerlund-Wikström, R. Virkola, K. Lähteenmäki, and T.K. Korhonen. (2007). Using every trick in the book: the Pla surface protease of Yersinia pestis. Adv Exp Med Biol 603: 268-278.

Yun, T.H. and J.H. Morrissey. (2009). Polyphosphate and omptins: novel bacterial procoagulant agents. J Cell Mol Med 13: 4146-4153.

Examples:

TC#NameOrganismal TypeExample
9.B.50.1.1

Outer membrane protease, OmpT (Hritonenko and Stathopoulos 2007).

Proteobacteria

OmpT of E. coli

 
9.B.50.1.2

OmpP protease (Hritonenko and Stathopoulos 2007).

Proteobacteria

OmpP of E. coli

 
9.B.50.1.3

PgtP protease (Kukkonen and Korhonen 2004).

Proteobacteria

PgtP of Salmonella enterica

 
9.B.50.1.4

Plasminogen activator, Pla (Korhonen et al. 2013).  The 3-d strucutre is known (PDB 4DCB).

Proteobacteria

Pla of Yersinia pestis

 
9.B.50.1.5

Outer membrane protease of 326 aas

Proteobacteria

OM protease of Desulfotalea psychrophila

 
9.B.50.1.6

Outer membrane protease (OmpT) of 344 aas

Spirochaetes

OmpT of Spirochaeta africana

 
9.B.50.1.7

Uncharacterized protein of 333 aas.

Spirochaetes

UP of Treponema brennaborense

 
9.B.50.1.8

Peptidase of 315 aas.

Fusobacteria

Peptidase of Fusobacterium ulcerans

 
9.B.50.1.9

Uncharacterized protein of 346 aas

Spirochaeta

UP of Leptospira interrogans

 
Examples:

TC#NameOrganismal TypeExample
9.B.50.2.1

Uncharacterized protein of 322 aas.  May be distantly related to 1.B.72.2.4.

Firmicutes

UP of Acetonema longum