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Structural basis for catalysis in a CDP-alcohol phosphotransferase

Author

Listed:
  • Giuliano Sciara

    (Columbia University)

  • Oliver B. Clarke

    (Columbia University)

  • David Tomasek

    (Columbia University)

  • Brian Kloss

    (New York Consortium on Membrane Protein Structure, New York Structural Biology Center)

  • Shantelle Tabuso

    (New York Consortium on Membrane Protein Structure, New York Structural Biology Center)

  • Rushelle Byfield

    (Columbia University)

  • Raphael Cohn

    (Columbia University)

  • Surajit Banerjee

    (Cornell University, NE-CAT, Advanced Photon Source)

  • Kanagalaghatta R. Rajashankar

    (Cornell University, NE-CAT, Advanced Photon Source)

  • Vesna Slavkovic

    (Mailman School of Public Health, Columbia University)

  • Joseph H. Graziano

    (Mailman School of Public Health, Columbia University)

  • Lawrence Shapiro

    (Columbia University)

  • Filippo Mancia

    (Columbia University)

Abstract

The CDP-alcohol phosphotransferase (CDP-AP) family of integral membrane enzymes catalyses the transfer of a substituted phosphate group from a CDP-linked donor to an alcohol acceptor. This is an essential reaction for phospholipid biosynthesis across all kingdoms of life, and it is catalysed solely by CDP-APs. Here we report the 2.0 Å resolution crystal structure of a representative CDP-AP from Archaeoglobus fulgidus. The enzyme (AF2299) is a homodimer, with each protomer consisting of six transmembrane helices and an N-terminal cytosolic domain. A polar cavity within the membrane accommodates the active site, lined with the residues from an absolutely conserved CDP-AP signature motif (D1xxD2G1xxAR…G2xxxD3xxxD4). Structures in the apo, CMP-bound, CDP-bound and CDP-glycerol-bound states define functional roles for each of these eight conserved residues and allow us to propose a sequential, base-catalysed mechanism universal for CDP-APs, in which the fourth aspartate (D4) acts as the catalytic base.

Suggested Citation

  • Giuliano Sciara & Oliver B. Clarke & David Tomasek & Brian Kloss & Shantelle Tabuso & Rushelle Byfield & Raphael Cohn & Surajit Banerjee & Kanagalaghatta R. Rajashankar & Vesna Slavkovic & Joseph H. G, 2014. "Structural basis for catalysis in a CDP-alcohol phosphotransferase," Nature Communications, Nature, vol. 5(1), pages 1-10, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5068
    DOI: 10.1038/ncomms5068
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    Cited by:

    1. Martin Centola & Katharina van Pee & Heidi Betz & Özkan Yildiz, 2021. "Crystal structures of phosphatidyl serine synthase PSS reveal the catalytic mechanism of CDP-DAG alcohol O-phosphatidyl transferases," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. Lie Wang & Ming Zhou, 2023. "Structure of a eukaryotic cholinephosphotransferase-1 reveals mechanisms of substrate recognition and catalysis," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    3. Zhenhua Wang & Meng Yang & Yufan Yang & Yonglin He & Hongwu Qian, 2023. "Structural basis for catalysis of human choline/ethanolamine phosphotransferase 1," Nature Communications, Nature, vol. 14(1), pages 1-8, December.

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