Structural basis for carotenoid cleavage by an archaeal carotenoid dioxygenase

Daruwalla, Anahita; Zhang, Jianye; Lee, Ho Jun; Khadka, Nimesh; Farquhar, Erik R.; Shi, Wuxian; von Lintig, Johannes; Kiser, Philip D.

doi:10.1073/pnas.2004116117

Structural basis for carotenoid cleavage by an archaeal carotenoid dioxygenase

Journal Article · Tue Aug 18 00:00:00 EDT 2020 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.2004116117· OSTI ID:1668655

^[1]; Zhang, Jianye ^[2]; ^[2]; Khadka, Nimesh ^[3]; ^[4]; Shi, Wuxian ^[5]; ^[3]; ^[6]

Univ. of California School of Medicine, Irvine, CA (United States); Case Western Reserve Univ. of Medicine, Cleveland, OH (United States)
Univ. of California School of Medicine, Irvine, CA (United States)
Case Western Reserve Univ. of Medicine, Cleveland, OH (United States)
Case Western Reserve Univ. of Medicine, Cleveland, OH (United States); Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)
Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)
Univ. of California School of Medicine, Irvine, CA (United States); Veterans Affairs Long Beach Healthcare System, Long Beach, CA (United States)

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 Candidatus Nitrosotalea devanaterra (NdCCD). Nd 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 Nd CCD revealed a tapered active site cavity markedly different from the broad active site observed for the retinal-forming Synechocystis apocarotenoid oxygenase ( Syn ACO) but similar to the vertebrate retinoid isomerase RPE65. The structure of Nd 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.

View Accepted Manuscript (DOE)

Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)

Grant/Contract Number:: SC0012704

OSTI ID:: 1668655

Alternate ID(s):: OSTI ID: 1659310

Report Number(s):: BNL--219888-2020-JAAM

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 33 Vol. 117; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

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