Structural insights into bifunctional thaumarchaeal crotonyl-CoA hydratase and 3-hydroxypropionyl-CoA dehydratase from Nitrosopumilus maritimus

Ebru Destan; Busra Yuksel; Bradley B Tolar; Esra Ayan; Sam Deutsch; Yasuo Yoshikuni; Soichi Wakatsuki; Christopher A Francis; Hasan DeMirci

doi:10.1038/s41598-021-02180-8

Structural insights into bifunctional thaumarchaeal crotonyl-CoA hydratase and 3-hydroxypropionyl-CoA dehydratase from Nitrosopumilus maritimus

Sci Rep. 2021 Nov 24;11(1):22849. doi: 10.1038/s41598-021-02180-8.

Authors

Ebru Destan¹, Busra Yuksel¹, Bradley B Tolar², Esra Ayan¹, Sam Deutsch³, Yasuo Yoshikuni⁴, Soichi Wakatsuki^{5

6}, Christopher A Francis⁷, Hasan DeMirci^{8

9}

Affiliations

¹ Department of Molecular Biology and Genetics, Koc University, 34450, Istanbul, Turkey.
² Department of Earth System Science, Stanford University, Stanford, CA, 94305, USA.
³ Nutcracker Therapeutics, Inc 5858 Horton Street, Suite 540, Emeryville, CA, 94608, USA.
⁴ The US Department of Energy, Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
⁵ Department of Structural Biology, Stanford University, Palo Alto, CA, 94305, USA. soichi.wakatsuki@stanford.edu.
⁶ Biosciences Division, SLAC National Laboratory, Menlo Park, CA, 94025, USA. soichi.wakatsuki@stanford.edu.
⁷ Department of Earth System Science, Stanford University, Stanford, CA, 94305, USA. caf@stanford.edu.
⁸ Department of Molecular Biology and Genetics, Koc University, 34450, Istanbul, Turkey. hdemirci@stanford.edu.
⁹ Stanford PULSE Institute, SLAC National Laboratory, Menlo Park, CA, 94025, USA. hdemirci@stanford.edu.

Abstract

The ammonia-oxidizing thaumarchaeal 3-hydroxypropionate/4-hydroxybutyrate (3HP/4HB) cycle is one of the most energy-efficient CO₂ fixation cycles discovered thus far. The protein encoded by Nmar_1308 (from Nitrosopumilus maritimus SCM1) is a promiscuous enzyme that catalyzes two essential reactions within the thaumarchaeal 3HP/4HB cycle, functioning as both a crotonyl-CoA hydratase (CCAH) and 3-hydroxypropionyl-CoA dehydratase (3HPD). In performing both hydratase and dehydratase activities, Nmar_1308 reduces the total number of enzymes necessary for CO₂ fixation in Thaumarchaeota, reducing the overall cost for biosynthesis. Here, we present the first high-resolution crystal structure of this bifunctional enzyme with key catalytic residues in the thaumarchaeal 3HP/4HB pathway.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Acyl Coenzyme A / metabolism*
Archaea / enzymology*
Archaea / genetics
Archaeal Proteins / chemistry
Archaeal Proteins / genetics
Archaeal Proteins / metabolism*
Carbon Dioxide / metabolism*
Catalysis
Crystallography, X-Ray
Enoyl-CoA Hydratase / chemistry
Enoyl-CoA Hydratase / genetics
Enoyl-CoA Hydratase / metabolism*
Models, Molecular
Protein Conformation
Structure-Activity Relationship
Substrate Specificity

Substances

Acyl Coenzyme A
Archaeal Proteins
Carbon Dioxide
3-hydroxybutyryl-coenzyme A
crotonyl-coenzyme A
Enoyl-CoA Hydratase

Grants and funding

P41 GM103393/GM/NIGMS NIH HHS/United States