6ra3

Structural basis for recognition and ring-cleavage of the Pseudomonas quinolone signal (PQS) by AqDC in complex with its product

spinqualitylabelsall models 6ra3, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ra3 is a 3 chain structure with sequence from "mycobacterium_abscessus_subsp._abscessus"_leao_et_al._2009 "mycobacterium abscessus subsp. abscessus" leao et al. 2009. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: JWH Gene: SAMEA2070698_02780, SAMEA2161603_04096, SAMEA2275805_05965 ("Mycobacterium abscessus subsp. abscessus" Leao et al. 2009) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The cofactor-less dioxygenase AqdC of Mycobacteroides abscessus catalyzes the cleavage and thus inactivation of the Pseudomonas quinolone signal (PQS, 2-heptyl-3-hydroxy-4(1H)-quinolone), which plays a central role in the regulation of virulence factor production by Pseudomonas aeruginosa. We present here the crystal structures of AqdC in its native state and in complex with the PQS cleavage product N-octanoylanthranilic acid, and of mutant AqdC proteins in complex with PQS. AqdC possesses an alpha/beta-hydrolase fold core domain with additional helices forming a cap domain. The protein is traversed by a bipartite tunnel, with a funnel-like entry section leading to an elliptical substrate cavity where PQS positioning is mediated by a combination of hydrophobic interactions and hydrogen bonds, with the substrate's C4 carbonyl and C3 hydroxyl groups tethered by His97 and the catalytic His246, respectively. The side chain of the AqdC-bound product extends deeper into the "alkyl tail section" of the tunnel than PQS, tentatively suggesting product exit via this part of the tunnel. AqdC prefers PQS over congeners with shorter alkyl substituents at C2. Kinetic data confirmed the strict requirement of the active-site base His246 for catalysis, and suggested that evolution of the canonical nucleophile/His/Asp catalytic triad of the hydrolases to an Ala/His/Asp triad is favorable for catalyzing dioxygenolytic PQS ring cleavage. Structural basis for recognition and ring-cleavage of the Pseudomonas quinolone signal (PQS) by AqdC, a mycobacterial dioxygenase of the alpha/beta-hydrolase fold family.,Wullich SC, Kobus S, Wienhold M, Hennecke U, Smits SHJ, Fetzner S J Struct Biol. 2019 Jun 19. pii: S1047-8477(19)30135-2. doi:, 10.1016/j.jsb.2019.06.006. PMID:31228546 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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