6VCH

Crystal structure of Nitrosotalea devanaterra carotenoid cleavage dioxygenase in complex with 3-hydroxy-beta-apo-14'-carotenal

Summary for 6VCH

• Entry DOI: 10.2210/pdb6vch/pdb
• Related: 6VCG
• Descriptor: carotenoid cleavage dioxygenase, COBALT (II) ION, (2E,4E,6E,8E,10E)-11-[(4R)-4-hydroxy-2,6,6-trimethylcyclohex-1-en-1-yl]-5,9-dimethylundeca-2,4,6,8,10-pentaenal, ... (6 entities in total)
• Functional Keywords: non-heme iron enzyme, carotenoid, apocarotenoid, mononuclear iron, beta propeller, rpe65, dioxygenase, oxidoreductase
• Biological source: Candidatus Nitrosotalea devanaterra
• Total number of polymer chains: 6
• Total formula weight: 325067.15

Authors

Daruwalla, A.,Shi, W.,Kiser, P.D. (deposition date: 2019-12-20, release date: 2020-07-08, Last modification date: 2023-10-11)

Primary citation

Daruwalla, A.,Zhang, J.,Lee, H.J.,Khadka, N.,Farquhar, E.R.,Shi, W.,von Lintig, J.,Kiser, P.D.
Structural basis for carotenoid cleavage by an archaeal carotenoid dioxygenase.
Proc.Natl.Acad.Sci.USA, 117:19914-19925, 2020

PubMed Abstract: Apocarotenoids are important signaling molecules generated from carotenoids through the action of carotenoid cleavage dioxygenases (CCDs). These enzymes have a remarkable ability to cleave carotenoids at specific alkene bonds while leaving chemically similar sites within the polyene intact. Although several bacterial and eukaryotic CCDs have been characterized, the long-standing goal of experimentally visualizing a CCD-carotenoid complex at high resolution to explain this exquisite regioselectivity remains unfulfilled. CCD genes are also present in some archaeal genomes, but the encoded enzymes remain uninvestigated. Here, we address this knowledge gap through analysis of a metazoan-like archaeal CCD from Nitrosotalea devanaterra (CCD). CCD was active toward β-apocarotenoids but did not cleave bicyclic carotenoids. It exhibited an unusual regiospecificity, cleaving apocarotenoids solely at the C14'-C13' alkene bond to produce β-apo-14'-carotenals. The structure of CCD revealed a tapered active site cavity markedly different from the broad active site observed for the retinal-forming apocarotenoid oxygenase (ACO) but similar to the vertebrate retinoid isomerase RPE65. The structure of CCD in complex with its apocarotenoid product demonstrated that the site of cleavage is defined by interactions along the substrate binding cleft as well as selective stabilization of reaction intermediates at the scissile alkene. These data on the molecular basis of CCD catalysis shed light on the origins of the varied catalytic activities found in metazoan CCDs, opening the possibility of modifying their activity through rational chemical or genetic approaches.

PubMed: 32747548
DOI: 10.1073/pnas.2004116117

Experimental method

X-RAY DIFFRACTION (2.35 Å)