Omptin proteins: an expanding family of outer membrane proteases in Gram-negative Enterobacteriaceae (Review)

Figures & data

Table I.  Characteristics of the proteins of the omptin family.

Protein	Host organism	Identity to OmpT (%)	Size of mature protein (kDa)	Roles in pathogenesis
OmpT	Escherichia coli K12	100	33.4	Cleaves proteamine, the antimicrobial peptide, secreted by the urinary tract epithelial cells; processes some autotransporter proteins
OmpP	Escherichia coli K12	73	33.1	Processes some autotransporter proteins
SopA/IcsPSopA2/SopA3	Shigella flexneri enteroinvasive E. coli Shigella dysenteriae	60	33.4	Cleaves IcsA autotransporter, ensuring polar localization of IcsA; required for proper actin-based motility inside host eukaryotic cells
PgtE/PgtE2	Salmonella enterica	50	32.8	Cleaves α-helical cationic antimicrobial peptides secreted by epithelial cells
Pla	Yersinia pestis	50	32.6	Activates plasmin; inactivates α2-antiplasmin (plasmin inhibitor); cleaves Complement C3 component; mediates bacterial adhesion to ECM of eukaryotic cells; mediates bacterial invasion into eukaryotic cells
PlaA	Erwinia pyrifoliae	47	32.3	N/A
Q8ZGQ6	Yersinia pestis	40	32.4	Contributes to infection establishment in C. elegans

Figure 1.  Crystal structure and membrane topology of OmpT (1I78). Adapted and reproduced with permission from reference [1]. (A) Front and side views of OmpT based on its crystal structure. (B) Topology model of OmpT. Amino acids in squares form β-strands. Periplasmic loops are labeled T1–T5. Loops exposed to the extracellular space are labeled L1–L5. The position of outer membrane is highlighted in gray. This Figure is reproduced in color in Molecular Membrane Biology online.

Table II.  Amino acids with the known functions among the omptin proteins.

	OmpT	OmpP	SopA 1/2/3	Pla/PlaA/AAN04526.1	PgtE/PgtE2	lpl2311	EAN05038.1	CAG37431.1	mlr6132	Q8ZGQ6/CAH20506.1	AAW85741.1	AAG31039
Catalytic amino acids
Asp 83	+	+	+	+	+	+	+	+	+	Asn	Glu	Ile
Asp 85	+	+	+	+	+	+	+	+	+	+	Arg	Gln
Asp 210	+	+	+	+	+	+	+	+	+	+	+	Ser
His 212	+	+	+	+	+	+	+	+	+	+	+	Ile
Active site amino acids
Glu 27	+	+	+	+	+	+	Ala	+	+	+	+	+
Ser 40	+	+	+	+	+	+	+	+	+	+	+	+
Leu 42	+	+	+	+	+	+	+	+	+	+	+	Lys
Met 81	+	+	+	+	+	+	+	+	+	+	His	Val
Asp 97	+	+	+	+	+	His	His	His	Asn	+	+	Gln
Ser 99	+	+	+	+	+	+	+	+	+	+	+	+
His 101	+	+	+	+	+	+	+	Asp	+	+	Ser	+
Ala 143	+	+	+	+	+	+	Ser	Ser	+	+	Asp	+
Tyr 150	+	+	+	+	+	+	+	+	+	+	+	+
Ile 170	+	+	+	+	+	+	+	+	+	Val	+	Val
Asp 208	+	+	+	+	+	+	+	+	Ala	Ala	+	+
Ser 223	+	+	Asp	Glu	Glu	Glu	Asp	Lys	Asp	Asp	Lys	Asp
Thr 263	+	+	+	+	+	+	+	+	Tyr	+	Met	Val
Ala 280	+	+	+	+	+	+	+	+	Ile	Ser	+	Asp
Ile 282	+	+	+	+	+	Leu	Ala	Gly	Gly	+	Leu	+
LPS Binding region
Tyr 134	+	+	+	+	+	+	Leu	Leu	Phe	+	Phe	Phe
Glu 136	+	+	+	+	+	Trp	Tyr	Gln	Tyr	+	Tyr	Lys
Arg 138	+	+	+	+	+	Ser	Asp	Asn	Ser	Asn	Gln	Asn
Arg 175	+	His	Leu	+	+	Lys	+	Trp	Lys	Lys	Glu	Asp
Lys 226	+	Ile	+	Ser	Glu	Asn	+	Asp	Glu	+	Glu	Thr

Table III.  Summary of preferable amino acids in the recognition site of OmpT substrate.

Position of substrate amino acid	Amino acids permitted in a descending order.	Comments
P6	Lys, Arg > >Asn, Gln > Ala.	Positively charged amino acids are preferred; acidic amino acids are not allowed.
P4	Arg, Lys > >Gly.	Positively charged amino acids are preferred; acidic amino acids are not allowed.
P3	Arg > Trp > Val
P2	Ala > Ile, Phe > Leu > Val > Pro > His > Gly > Arg.	Broad tolerance; acidic amino acids are not allowed.
P1	Arg or Lys.	Highly conserved.
P1’	Lys > Ile > His > Arg.	Acidic amino acids are not allowed.
P2’	Ile, Val > Ala.	Amino acids with small side chains are preferred.
P3’	Trp > Arg > Thr.	Amino acids with large side chains are preferred.

Figure 2.  Phylogenetic tree of the omptin family members from theA26 family from the MEROPS database [56]. Scale bar refers to time in million years. MEGA3 software and UPGMA method were used to contract the tree [68].

Vandeputte-Rutten L, Kramer RA, Kroon J, Dekker N, Egmond MR, Gros P. Crystal structure of the outer membrane protease OmpT from Escherichia coli suggests a novel catalytic site. Embo J 2001; 20: 5033–5039

 PubMed Web of Science ®Google Scholar

Rawlings ND, Morton FR, Barrett AJ. MEROPS: the peptidase database. Nucleic Acids Res 2006; 34: D270–272

 PubMed Web of Science ®Google Scholar

Kumar S, Tamura K, Nei M. MEGA3: Integrated software for molecular evolutionary genetics analysis and sequence alignment. Brief Bioinform 2004; 5: 150–163

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