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Title: Structural basis for carotenoid cleavage by an archaeal carotenoid dioxygenase

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 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 scissilemore » 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.« less

Authors:
ORCiD logo [1];  [2]; ORCiD logo [2];  [3]; ORCiD logo [4];  [5]; ORCiD logo [3]; ORCiD logo [6]
  1. Univ. of California School of Medicine, Irvine, CA (United States); Case Western Reserve Univ. of Medicine, Cleveland, OH (United States)
  2. Univ. of California School of Medicine, Irvine, CA (United States)
  3. Case Western Reserve Univ. of Medicine, Cleveland, OH (United States)
  4. 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)
  5. Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)
  6. Univ. of California School of Medicine, Irvine, CA (United States); Veterans Affairs Long Beach Healthcare System, Long Beach, CA (United States)
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1668655
Report Number(s):
BNL-219888-2020-JAAM
Journal ID: ISSN 0027-8424
Grant/Contract Number:  
SC0012704
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 117; Journal Issue: 33; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Daruwalla, Anahita, Zhang, Jianye, Lee, Ho Jun, Khadka, Nimesh, Farquhar, Erik R., Shi, Wuxian, von Lintig, Johannes, and Kiser, Philip D. Structural basis for carotenoid cleavage by an archaeal carotenoid dioxygenase. United States: N. p., 2020. Web. doi:10.1073/pnas.2004116117.
Daruwalla, Anahita, Zhang, Jianye, Lee, Ho Jun, Khadka, Nimesh, Farquhar, Erik R., Shi, Wuxian, von Lintig, Johannes, & Kiser, Philip D. Structural basis for carotenoid cleavage by an archaeal carotenoid dioxygenase. United States. doi:10.1073/pnas.2004116117.
Daruwalla, Anahita, Zhang, Jianye, Lee, Ho Jun, Khadka, Nimesh, Farquhar, Erik R., Shi, Wuxian, von Lintig, Johannes, and Kiser, Philip D. Tue . "Structural basis for carotenoid cleavage by an archaeal carotenoid dioxygenase". United States. doi:10.1073/pnas.2004116117.
@article{osti_1668655,
title = {Structural basis for carotenoid cleavage by an archaeal carotenoid dioxygenase},
author = {Daruwalla, Anahita and Zhang, Jianye and Lee, Ho Jun and Khadka, Nimesh and Farquhar, Erik R. and Shi, Wuxian and von Lintig, Johannes and Kiser, Philip D.},
abstractNote = {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.},
doi = {10.1073/pnas.2004116117},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
issn = {0027-8424},
number = 33,
volume = 117,
place = {United States},
year = {2020},
month = {8}
}

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