1.B.25 The Outer Membrane Porin (Opr) Family

The Opr family includes a number of porins in Pseudomonas species and other Gram-negative bacteria that appear to exhibit a variety of substrate selectivities. Thus, OprD2 of P. aeruginosa is specific for cationic amino acids, peptides and antibiotics, while PhaK is specific for phenolic compounds. GusC of E. coli is a 'membrane accessory protein' that facilitates uptake of glucuronides via the GusB permease. Many other specificities have been assigned (Tamber et al., 2006).

Tamber et al. (2006) have characterized several of the 19 paralogues in Pseudomonas aeruginosa. They fall into two fairly closely related phylogenetic clusters. Members of one, including OprD, exhibit specificities for amino acids and their derivatives while the other, including PhaK, are specific for organic acids. Another group of functionally characterized porins, determined by Tamber et al. (2006), are described in the table of the Opr family homologues by these authors.

In P. aeruginosa, the majority of small molecules are taken up by members of the OprD outer membrane protein family. Eren et al. (2012) showed that OprD channels require a carboxyl group in the substrate for efficient transport. They have renamed the family Occ, for outer membrane carboxylate channels. Occ channels can be divided into two subfamilies, based on their very different substrate specificities.

Liu et al. (2012) reported that the OccK proteins exhibit fairly distinct unitary conductance values including low (~40-100 pS) and medium (~100-380 pS) conductances. These proteins showed diverse single-channel dynamics of current gating transitions, revealing one (OccK3), two (OccK4, OccK5 and OccK6) and three (OccK1, OccK2 and OccK7) open sub-state kinetics with functionally distinct conformations. Anion selectivity is a conserved trait among the members of the OccK subfamily, confirming the presence of a net pool of positively charged residues within their central constriction.

The generalized transport reaction catalyzed by members of the Opr family is:

Substrate (out) substrate (periplasm)



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

 

References:

Benkerrou, D., and M. Ceccarelli,. (2018). Free energy calculations and molecular properties of substrate translocation through OccAB porins. Phys Chem Chem Phys 20: 8533-8546.

Biswas, S., M.M. Mohammad, L. Movileanu, and B. van den Berg. (2008). Crystal structure of the outer membrane protein OpdK from Pseudomonas aeruginosa. Structure 16: 1027-1035.

Cavalcanti, F.L., C.R. Mirones, E.R. Paucar, L.&.#.1.9.3.;. Montes, T.C. Leal-Balbino, M.M. Morais, L. Martínez-Martínez, and A.A. Ocampo-Sosa. (2015). Mutational and acquired carbapenem resistance mechanisms in multidrug resistant Pseudomonas aeruginosa clinical isolates from Recife, Brazil. Mem Inst Oswaldo Cruz 110: 1003-1009.

Choudhary, A., H. Purohit, and P.S. Phale. (2017). Benzoate transport in Pseudomonas putida CSV86. FEMS Microbiol. Lett. 364:.

Clark, T.J., C. Momany, and E.L. Neidle. (2002). The benPK operon, proposed to play a role in transport, is part of a regulon for benzoate catabolism in Acinetobacter sp. strain ADP1. Microbiology 148: 1213-1223.

Eren, E., J. Vijayaraghavan, J. Liu, B.R. Cheneke, D.S. Touw, B.W. Lepore, M. Indic, L. Movileanu, and B. van den Berg. (2012). Substrate specificity within a family of outer membrane carboxylate channels. PLoS Biol 10: e1001242.

Fluit, A.C., R.J. Rentenaar, M.B. Ekkelenkamp, T.T. Severs, A.M.C. Mavinkurve-Groothuis, M.R.C. Rogers, M.C.A. Bruin, and T.F.W. Wolfs. (2019). Fatal Carbapenem Resistance Development in Pseudomonas Aeruginosa Under Meropenem Monotherapy, Caused by Mutations in the OprD Outer Membrane Porin. Pediatr Infect Dis J 38: 398-399.

Fowler, R.C. and N.D. Hanson. (2015). The OpdQ porin of Pseudomonas aeruginosa is regulated by environmental signals associated with cystic fibrosis including nitrate-induced regulation involving the NarXL two-component system. Microbiologyopen. [Epub: Ahead of Print]

Knopp, M. and D.I. Andersson. (2015). Amelioration of the Fitness Costs of Antibiotic Resistance Due To Reduced Outer Membrane Permeability by Upregulation of Alternative Porins. Mol Biol Evol 32: 3252-3263.

Lee, J., K.R. Pothula, U. Kleinekathöfer, and W. Im. (2018). Simulation Study of Occk5 Functional Properties in Pseudomonas aeruginosa Outer Membranes. J Phys Chem B 122: 8185-8192.

Liang, W.-J., K.J. Wilson, H. Xie, J. Knol, S. Suzuki, N.G. Rutherford, P.J.F. Henderson, and R.A. Jefferson. (2005). The gusBC genes of Escherichia coli encode a glucuronide transport system. J. Bacteriol. 187: 2377-2385.

Liu, J., E. Eren, J. Vijayaraghavan, B.R. Cheneke, M. Indic, B. van den Berg, and L. Movileanu. (2012). OccK channels from Pseudomonas aeruginosa exhibit diverse single-channel electrical signatures but conserved anion selectivity. Biochemistry 51: 2319-2330.

Ochs, M.M., C.-D. Lu, R.E.W. Hancock, and A.T. Abdelal. (1999). Amino acid-mediated induction of the basic amino acid-specific outer membrane porin OprD from Pseudomonas aeruginosa. J. Bacteriol. 181:5426-5432.

Okamoto, K., N. Gotoh, H. Tsujimoto, H. Yamada, E. Yoshihara, T. Nakae, and T. Nishino. (1999). Molecular cloning and characterization of the oprQ gene coding for outer membrane protein OprE3 of Pseudomonas aeruginosa. Microbiol Immunol 43: 297-301.

Olivera, E.R., B. Miñambres, B. Garcìa, M.A. Moreno, A, Ferràndez, E. Dìaz, J.L. Garcìa, and J.M. Luengo. (1998). Molecular characterization of the phenylacetic acid catabolic pathway in Pseudomonas putida U: the phenylacetyl-CoA catabolon. Proc. Natl. Acad. Sci. USA 95: 6419-6424.

Paulsson M., Singh B., Al-Jubair T., Su YC., Hoiby N. and Riesbeck K. (2015). Identification of outer membrane Porin D as a vitronectin-binding factor in cystic fibrosis clinical isolates of Pseudomonas aeruginosa. J Cyst Fibros. 14(5):600-7.

Rivera, S.L., E. Vargas, M.I. Ramírez-Díaz, J. Campos-García, and C. Cervantes. (2008). Genes related to chromate resistance by Pseudomonas aeruginosa PAO1. Antonie Van Leeuwenhoek 94: 299-305.

Samanta, S., I. Bodrenko, S. Acosta-Gutiérrez, T. D''Agostino, M. Pathania, I. Ghai, C. Schleberger, D. Bumann, R. Wagner, M. Winterhalter, B. van den Berg, and M. Ceccarelli. (2018). Getting Drugs through Small Pores: Exploiting the Porins Pathway in Pseudomonas aeruginosa. ACS Infect Dis. [Epub: Ahead of Print]

Shen, J.L. and Y.P. Fang. (2015). Detection of drug-resistance mechanism of Pseudomonas aeruginosa developing from a sensitive strain to a persister during carbapenem treatment. Genet Mol Res 14: 6723-6732.

Tamber, S., E. Maier, R. Benz, and R.E. Hancock. (2007). Characterization of OpdH, a Pseudomonas aeruginosa porin involved in the uptake of tricarboxylates. J. Bacteriol. 189: 929-939.

Tamber, S., M.M. Ochs, and R.E. Hancock. (2006). Role of the novel OprD family of porins in nutrient uptake in Pseudomonas aeruginosa. J. Bacteriol. 188: 45-54.

Trias J. and H. Nikaido. (1990). Protein D2 channel of the Pseudomonas aeruginosa outer membrane has a binding site for basic amino acids and peptides. J. Biol. Chem. 265: 15680-15684.

Tsai, Y.L., M.C. Wang, P.R. Hsueh, M.C. Liu, R.M. Hu, Y.J. Wu, and S.J. Liaw. (2015). Overexpression of an outer membrane protein associated with decreased susceptibility to carbapenems in Proteus mirabilis. PLoS One 10: e0120395.

Wang, Y., X. Zhao, B. Sun, H. Yu, and X. Huang. (2012). Molecular dynamics simulation study of the vanillate transport channel of Opdk. Arch Biochem Biophys 524: 132-139.

Yang, H., L. Huang, P.A. Barnie, Z. Su, Z. Mi, J. Chen, V. Aparna, D. Kumar, and H. Xu. (2015). Characterization and distribution of drug resistance associated β-lactamase, membrane porin and efflux pump genes in MDR A. baumannii isolated from Zhenjiang, China. Int J Clin Exp Med 8: 15393-15402.

Zahn, M., S.P. Bhamidimarri, A. Baslé, M. Winterhalter, and B. van den Berg. (2016). Structural Insights into Outer Membrane Permeability of Acinetobacter baumannii. Structure 24: 221-231.

Examples:

TC#NameOrganismal TypeExample
1.B.25.1.1

OprD2; OccD1; porin D transports cationic amino acids, peptides and other compounds: lysine, arginine, histidine, ornithine, basic di- and tri-peptides, and cationic antibiotics such as imipenem (n-formimidoylthienamycin) and other penems and carbapenems (Tamber et al., 2006).  The 3-d structure and drugs transported are known (4FOZ; Parkin and Khalid 2014).  OprD is the vitronectin receptor. Vitronectin enhances P. aeruginosa adhesion to host epithelial cells and thereby enhances virulence (Paulsson et al. 2015).  Loss promotes carbapenem resistance (Shen and Fang 2015; Cavalcanti et al. 2015). Loss results in resistance to  meropenem (Fluit et al. 2019).

Proteobacteria

OprD2 of Pseudomonas aeruginosa (P32722)

 
1.B.25.1.10

A tricarboxylate transporting porin, OdpH (Occk5) induced by and transports cis-aconitate, isocitrate and citrate; exhibits a large single channel conductance (Tamber et al., 2006; 2007).  This porin exhibits a high degree of anion selectivity, and the outer core and O-antigens of LPS sterically occlude the channel entrance to decrease the diffusion constants of approaching ions  (Lee et al. 2018).

Gram-negative bacteria

OpdH of Pseudomonas aeruginosa (AAG04144)

 
1.B.25.1.11OpdB proline-selective porin (Tamber et al., 2006) Gram-negative bacteriaOpdB of Pseudomonas aeruginosa (AAG06088)
 
1.B.25.1.12

OpdC or OccD2 histidine-selective porin (Tamber et al., 2006).  The 3-D structure and substrate spcificities are known (PDB 3SY9; Eren et al. 2012).

Proteobacteria

OpdC of Pseudomonas aeruginosa (AAG03552)

 
1.B.25.1.13

Chitoporin, ChiP or YbfM of 468 aas. Takes up chitosugars such as chitobiose.  It also plays a role in carbapenem (imipenem) resistance.  The orthologue in Proteus mirabilis is ImpR, and that in Salmonella species is YbfM. It is subject to regulation by the small RNA, MicM (Tsai et al. 2015).  Loss of OmpC and OmpF results in poor growth, by expression of chiP restores growth (Knopp and Andersson 2015).

Gram-negative bacteria

ChiP of E. coli (P75733)

 
1.B.25.1.14

OdpF (OccK2) glucuronate-selective porin; may also transport benzoate and vanillate (Eren et al., 2012). 3-d structure is known (3SZD).

Gram-negative bacteria

OdpF of Pseudomonas aeruginosa (Q9I6P8)

 
1.B.25.1.15Outer membrane porin

Gram-negative bacteria

Ftrac_3105 of Marivirga tractuosa
 
1.B.25.1.16Outer membrane porin

Gram-negative bacteria

Tint_2055 of Thiomonas intermedia
 
1.B.25.1.17Outer membrane porin

Gram-negative bacteria

Sdel_0469 of Sulfurospirillum deleyianum
 
1.B.25.1.18Outer membrane porin, OprD family

Gram-negative bacteria

SULAZ_1441 of Sulfurihydrogenibium azorense
 
1.B.25.1.19Outer membrane porin, OprD family

Gram-negative bacteria

PROVRUST_07396 of Providencia rustigianii DSM 4541
 
1.B.25.1.2

OprE1 (OprE; OccK8) porin (anaerobically induced). May participate in chromate resistance (Rivera et al., 2008). The high-resolution X-ray structure and electrophysiology highlight a very narrow pore. However, transport of natural amino acids and antibiotics, among them ceftazidime, has been demonstrated (Samanta et al. 2018). As in general porins, the internal electric field favors the translocation of polar molecules by gainful energy compensation in the central constriction region. The comparatively narrow pore can undergo a substrate-induced expansion to accommodate relatively large-sized substrates (Samanta et al. 2018).

Gram-negative bacteria

OprE1 of Pseudomonas aeruginosa (Q51510)

 
1.B.25.1.20Outer membrane porin

Gram-negative bacteria

Sulku_2564 of Sulfuricurvum kujiense
 
1.B.25.1.21Outer membrane porin

Gram-negative bacteria

Atc_1106 of Acidithiobacillus caldus
 
1.B.25.1.22Outer membrane porin

Gram-negative bacteria

Sdel_0019 of Sulfurospirillum deleyianum
 
1.B.25.1.23Outer membrane porin, OprD family

Gram-negative bacteria

Dsui_2952 of Azospira oryzae
 
1.B.25.1.24Outer membrane porin, OprD family

Gram-negative bacteria

CBGD1_2399 of Campylobacterales bacterium GD 1
 
1.B.25.1.25Uncharacterized protein

Gram-negative bacteria

SMGD1_0130 of Sulfurimonas gotlandica GD1
 
1.B.25.1.26Outer membrane porin

Gram-negative bacteria

Sulku_1154 of Sulfuricurvum kujiense
 
1.B.25.1.27Outer membrane porin

Gram-negative bacteria

Sputcn32_0255 of Shewanella putrefaciens
 
1.B.25.1.28Putative outer membrane porin

Gram-negative bacteria

SMGD1_2744 of Sulfurimonas gotlandica GD1

 
1.B.25.1.29Outer membrane porin

Gram-negative bacteria

Sdel_2087 of Sulfurospirillum deleyianum
 
1.B.25.1.3

OprE3 (OprQ) porin (Okamoto et al. 1999).

Gram-negative bacteria

OprE3 of Pseudomonas aeruginosa (O24779)

 
1.B.25.1.30Outer membrane porinNoneSulku_1034 of Sulfuricurvum kujiense
 
1.B.25.1.31

Putative porin

γ-Proteobacteria

Putative porin of Shewanella sediminis

 
1.B.25.1.32

Outer membrane tyrosine-specific porin, OpdT (Tamber et al. 2006).

Proteobacteria

OpdT of Pseudomonas aeruginosa

 
1.B.25.1.33

Putative porin


Aquificae

Porin of Sulfurihydrogenibium azorense

 
1.B.25.1.34

The outer membrane porin, OdpQ of 421 aas.  opdQ is transcriptionally repressed under low oxygen but increased in the presence of nitrate. The nitrate-induced regulation is dependent on NarL via the NarXL two-component system. In addition, NaCl-induced osmotic stress increases OpdQ production among most of the clinical strains evaluated (Fowler and Hanson 2015).

OdpQ of Pseudomonas aeruginosa

 
1.B.25.1.35

Benzoate-specific porin protein of 397 aas and 1 N-terminal TMS, BenF (Choudhary et al. 2017).

BenF of Pseudomonas putida

 
1.B.25.1.36

BenP porin (Clark et al. 2002).  Probably transports aromatic compounds such as benzoate for degradation.

Proteobacteria

BenP of Acinetobacter sp.ADP1 (Acinetobacter baylyi)

 
1.B.25.1.37

Putative porin of 430 aas and 1 N-terminal TMS, NicP.

NicP of Pseudomonas putida

 
1.B.25.1.38

OprD or OccAB1 of 418 aas and 1 N-terminal TMS.  The 3-d structure has been determined for 4 similar porins, OccAB1 - 4 (Zahn et al. 2016). Probably allows the uptake of small molecules including sugars, amino acids and some antibiotics. The transport properties have been studied (Benkerrou and Ceccarelli 2018).

OprD of Acinetobacter baumannii

 
1.B.25.1.4

PhaK phenylacetate/organic acid porin

Gram-negative bacteria PhaK of Pseudomonas putida (O84986)
 
1.B.25.1.5

GusC (UidC) putative glucuronide porin (Liang et al., 2005).  Reported to enhance the activity of the UidB (GusB) glucuronide transporter (TC# 2.A.2.1.5). Glucuronide transport does not occur in strain K12 due to a variant at position 100 of the UidB protein.

Gram-negative bacteria

GusC of E. coli (Q47706)

 
1.B.25.1.6

Vanillate trafficing porin, VanP. 85% identical to OprD of Acinetobacter baumannii which when mutated confers MDR (Yang et al. 2015).

Gram-negative bacteria

VanP of Acinetobacter sp. ADP1 (Q6FDI3)

 
1.B.25.1.7OpdO pyroglutamate-specific porin (Tamber et al., 2006)Gram-negative bacteriaOpdO of Pseudomonas aeruginosa (AAG05501)
 
1.B.25.1.8

Anion-selective OpdK (OccK1 or OpdK) benzoate/vanillate-selective porin (Tamber et al., 2006Eren et al., 2012; Liu et al. 2012). The structure of the OpdK porin, specific for vanillate and related small aromatic acids, has been solved by x-ray crystallography (3SYS_A). It is a labile trimer with monomers of an 18 β-stranded barrel and with an inner diameter of 8Å (Biswas et al., 2008). Other substrates transported (but less well) include 4-nitrobenzoate, caproate, octanoate, carbenicillin, cefoxitin, tetracycline antibiotics, and carbapenem antibioitics (imipenem and meropenem) (Eren et al., 2012).  Molecular dynamic simulations and mutant analyses have been reported (Wang et al. 2012).

Gram-negative bacteria

OpdK of Pseudomonas aeruginosa (AAG08283)

 
1.B.25.1.9OpdP glycine-glutamate-selective porin (Tamber et al., 2006)Gram-negative bacteriaOpdP of Pseudomonas aeruginosa (AAG07889)
 
Examples:

TC#NameOrganismal TypeExample
1.B.25.2.1

Putative porin of 278 aas

Lentisphaerae

PP of Lentisphaera araneosa

 
1.B.25.2.2

Uncharacterized outer membrane porin of 388 aas and 1 N-terminal TMS.

OMP of Sulfurospirillum barnesii

 
1.B.25.2.3

Putative porin of 402 aas. 

Porin of Arcobacter porcinus]

 
Examples:

TC#NameOrganismal TypeExample