PDBsum entry 6lpy

Oxidoreductase

PDB id: 6lpy

Contents

Protein chains

607 a.a.

Ligands

FAD ×2

BUA-COA ×2

Waters ×1220

PDB id:

6lpy

Name:

Oxidoreductase

Title:

Crystal structure of e447a acyl-coa dehydrogenase fade5 mutant from mycobacteria smegmatis in complex with c4coa

Structure:

Acyl-coa dehydrogenase. Chain: a, b. Engineered: yes. Mutation: yes

Source:

Mycobacterium smegmatis. Organism_taxid: 1772. Gene: fade5, ers451418_00380. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.90Å R-factor: 0.159 R-free: 0.201

Authors:

X.Liu,X.B.Chen

Key ref:

X.Chen et al. (2020). Structural basis for the broad substrate specificity of two acyl-CoA dehydrogenases FadE5 from mycobacteria. Proc Natl Acad Sci U S A, 117, 16324-16332. PubMed id: 32601219 DOI: 10.1073/pnas.2002835117

Date:

12-Jan-20 Release date: 01-Jul-20

Protein chains

Q3L887  (Q3L887_MYCS2) -  Broad-specificity linear acyl-CoA dehydrogenase FadE5 from Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155)

Seq: 611 a.a.

Struc: 607 a.a.*

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

Enzyme reactions

• Enzyme class 2: E.C.1.3.8.1 - short-chain acyl-CoA dehydrogenase.
• Reaction: a short-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H⁺ = a short-chain (2E)-enoyl-CoA + reduced [electron- transfer flavoprotein]

Butanoyl-CoA (Bound ligand (Het Group name = COA) matches with 90.57% similarity) + electron-transfer flavoprotein = 2-butenoyl-CoA + reduced electron-transfer flavoprotein

• Cofactor: FAD

FAD (Bound ligand (Het Group name = FAD) corresponds exactly)

• Enzyme class 3: E.C.1.3.8.7 - medium-chain acyl-CoA dehydrogenase.
• Reaction: a medium-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H⁺ = a medium-chain (2E)-enoyl-CoA + reduced [electron- transfer flavoprotein]
• Enzyme class 4: E.C.1.3.8.8 - long-chain-acyl-CoA dehydrogenase.
• Reaction: a long-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H⁺ = a long-chain (2E)-enoyl-CoA + reduced [electron- transfer flavoprotein]
• Cofactor: FAD

FAD (Bound ligand (Het Group name = FAD) corresponds exactly)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

DOI no: 10.1073/pnas.2002835117

Proc Natl Acad Sci U S A 117:16324-16332 (2020)

PubMed id: 32601219

Structural basis for the broad substrate specificity of two acyl-CoA dehydrogenases FadE5 from mycobacteria.

X.Chen, J.Chen, B.Yan, W.Zhang, L.W.Guddat, X.Liu, Z.Rao.

ABSTRACT

FadE, an acyl-CoA dehydrogenase, introduces unsaturation to carbon chains in lipid metabolism pathways. Here, we report that FadE5 from Mycobacterium tuberculosis (MtbFadE5) and Mycobacterium smegmatis (MsFadE5) play roles in drug resistance and exhibit broad specificity for linear acyl-CoA substrates but have a preference for those with long carbon chains. Here, the structures of MsFadE5 and MtbFadE5, in the presence and absence of substrates, have been determined. These reveal the molecular basis for the broad substrate specificity of these enzymes. FadE5 interacts with the CoA region of the substrate through a large number of hydrogen bonds and an unusual π-π stacking interaction, allowing these enzymes to accept both short- and long-chain substrates. Residues in the substrate binding cavity reorient their side chains to accommodate substrates of various lengths. Longer carbon-chain substrates make more numerous hydrophobic interactions with the enzyme compared with the shorter-chain substrates, resulting in a preference for this type of substrate.