PDBsum entry 6ig2

Transferase

PDB id: 6ig2

Contents

Protein chains

272 a.a.

Ligands

CTP

Waters ×216

PDB id:

6ig2

Name:

Transferase

Title:

Structure of mitochondrial cdp-dag synthase tam41 complexed with ctp, delta 74, f240a

Structure:

Phosphatidate cytidylyltransferase, mitochondrial. Chain: a, b, c, d. Synonym: tam41, cdp-diacylglycerol synthase,cdp-dag synthase, mitochondrial translocator assembly and maintenance protein 41 homolog. Engineered: yes. Mutation: yes

Source:

Schizosaccharomyces pombe (strain 972 / atcc 24843). Fission yeast. Organism_taxid: 284812. Strain: 972 / atcc 24843. Gene: tam41, spbc1a4.06c. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.88Å R-factor: 0.219 R-free: 0.259

Authors:

H.Z.Jiao,Y.Yin,Z.F.Liu

Key ref:

H.Jiao et al. (2019). Structures of the Mitochondrial CDP-DAG Synthase Tam41 Suggest a Potential Lipid Substrate Pathway from Membrane to the Active Site. Structure, 27, 1258. PubMed id: 31178220 DOI: 10.1016/j.str.2019.04.017

Date:

23-Sep-18 Release date: 10-Jul-19

Protein chains

O74339  (TAM41_SCHPO) -  Phosphatidate cytidylyltransferase, mitochondrial from Schizosaccharomyces pombe (strain 972 / ATCC 24843)

Seq: 393 a.a.

Struc: 272 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.7.7.41 - phosphatidate cytidylyltransferase.
• Reaction: a 1,2-diacyl-sn-glycero-3-phosphate + CTP + H⁺ = a CDP-1,2-diacyl- sn-glycerol + diphosphate

1,2-diacyl-sn-glycero-3-phosphate + CTP (Bound ligand (Het Group name = CTP) corresponds exactly) + H(+) = CDP-1,2-diacyl- sn-glycerol + diphosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/j.str.2019.04.017

Structure 27:1258 (2019)

PubMed id: 31178220

Structures of the Mitochondrial CDP-DAG Synthase Tam41 Suggest a Potential Lipid Substrate Pathway from Membrane to the Active Site.

H.Jiao, Y.Yin, Z.Liu.

ABSTRACT

In mitochondria, CDP-diacylglycerol (CDP-DAG) is a crucial precursor for cardiolipin biosynthesis. Mitochondrial CDP-DAG is synthesized by the translocator assembly and maintenance protein 41 (Tam41) through an elusive process. Here we show that Tam41 adopts sequential catalytic mechanism, and report crystal structures of the bulk N-terminal region of Tam41 from Schizosaccharomyces pombe in the apo and CTP-bound state. The structure reveals that Tam41 contains a nucleotidyltransferase (NTase) domain and a winged helix domain. CTP binds to an "L"-shaped pocket sandwiched between the two domains. Rearrangement of a loop region near the active site is essential for opening the CTP-binding pocket. Docking of phosphatidic acid/CDP-DAG in the structure suggests a lipid entry/exit pathway connected to the "L"-shaped pocket. The C-terminal region of SpTam41 contains a positively charged amphipathic helix crucial for membrane association and participates in binding phospholipids. These results provide detailed insights into the mechanism of CDP-DAG biosynthesis in mitochondria.