8EHD

Structure of Tannerella forsythia potempin E

Summary for 8EHD

• Entry DOI: 10.2210/pdb8ehd/pdb
• Related: 8EHC
• Descriptor: Potempin E (PotE), 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID (3 entities in total)
• Functional Keywords: metallopeptidase inhibitor, hydrolase, hydrolase inhibitor
• Biological source: Tannerella forsythia
• Total number of polymer chains: 1
• Total formula weight: 15075.58

Authors

Gomis-Ruth, F.X. (deposition date: 2022-09-14, release date: 2022-12-21, Last modification date: 2024-10-09)

Primary citation

Ksiazek, M.,Goulas, T.,Mizgalska, D.,Rodriguez-Banqueri, A.,Eckhard, U.,Veillard, F.,Waligorska, I.,Benedyk-Machaczka, M.,Sochaj-Gregorczyk, A.M.,Madej, M.,Thogersen, I.B.,Enghild, J.J.,Cuppari, A.,Arolas, J.L.,de Diego, I.,Lopez-Pelegrin, M.,Garcia-Ferrer, I.,Guevara, T.,Dive, V.,Zani, M.L.,Moreau, T.,Potempa, J.,Gomis-Ruth, F.X.
A unique network of attack, defence and competence on the outer membrane of the periodontitis pathogen Tannerella forsythia.
Chem Sci, 14:869-888, 2023

PubMed Abstract: Periodontopathogenic uniquely secretes six peptidases of disparate catalytic classes and families that operate as virulence factors during infection of the gums, the KLIKK-peptidases. Their coding genes are immediately downstream of novel ORFs encoding the 98-132 residue potempins (Pot) A, B1, B2, C, D and E. These are outer-membrane-anchored lipoproteins that specifically and potently inhibit the respective downstream peptidase through stable complexes that protect the outer membrane of , as shown . Remarkably, PotA also contributes to bacterial fitness and specifically inhibits matrix metallopeptidase (MMP) 12, a major defence component of oral macrophages, thus featuring a novel and highly-specific physiological MMP inhibitor. Information from 11 structures and high-confidence homology models showed that the potempins are distinct β-barrels with either a five-stranded OB-fold (PotA, PotC and PotD) or an eight-stranded up-and-down fold (PotE, PotB1 and PotB2), which are novel for peptidase inhibitors. Particular loops insert like wedges into the active-site cleft of the genetically-linked peptidases to specifically block them either a new "bilobal" or the classic "standard" mechanism of inhibition. These results discover a unique, tightly-regulated proteolytic armamentarium for virulence and competence, the KLIKK-peptidase/potempin system.

PubMed: 36755705
DOI: 10.1039/d2sc04166a

Experimental method

X-RAY DIFFRACTION (1.8 Å)