PDBsum entry 4z0m

Lyase

PDB id: 4z0m

Contents

Protein chains

241 a.a.

Waters ×548

PDB id:

4z0m

Name:

Lyase

Title:

Echa5 mycobacterium tuberculosis

Structure:

Enoyl-coa hydratase. Chain: a, b, c. Synonym: enoyl-coa hydratase echa5,probable enoyl-coa hydratase echa5. Engineered: yes. Other_details: chain a of echa5 protein from mycobacterium tuberculosis

Source:

Mycobacterium tuberculosis h37rv. Organism_taxid: 83332. Strain: h37rv. Gene: echa5, rv0675. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.97Å R-factor: 0.169 R-free: 0.195

Authors:

S.Chaudhary,R.S.Gokhale

Key ref:

S.Srivastava et al. (2015). Unsaturated Lipid Assimilation by Mycobacteria Requires Auxiliary cis-trans Enoyl CoA Isomerase. Chem Biol, 22, 1577-1587. PubMed id: 26628360 DOI: 10.1016/j.chembiol.2015.10.009

Date:

26-Mar-15 Release date: 03-Feb-16

Protein chains

I6Y4E8  (I6Y4E8_MYCTU) -  Probable enoyl-CoA hydratase EchA5 (Enoyl hydrase) (Unsaturated acyl-CoA hydratase) (Crotonase) from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

Seq: 263 a.a.

Struc: 241 a.a.

Enzyme reactions

• Enzyme class: E.C.4.2.1.17 - enoyl-CoA hydratase.
• Reaction:
  1. a 4-saturated-(3S)-3-hydroxyacyl-CoA = a (3E)-enoyl-CoA + H2O
  2. a (3S)-3-hydroxyacyl-CoA = a (2E)-enoyl-CoA + H2O

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

Key reference

DOI no: 10.1016/j.chembiol.2015.10.009

Chem Biol 22:1577-1587 (2015)

PubMed id: 26628360

Unsaturated Lipid Assimilation by Mycobacteria Requires Auxiliary cis-trans Enoyl CoA Isomerase.

S.Srivastava, S.Chaudhary, L.Thukral, C.Shi, R.D.Gupta, R.Gupta, K.Priyadarshan, A.Vats, A.S.Haque, R.Sankaranarayanan, V.T.Natarajan, R.Sharma, C.C.Aldrich, R.S.Gokhale.

ABSTRACT

Mycobacterium tuberculosis (Mtb) can survive in hypoxic necrotic tissue by assimilating energy from host-derived fatty acids. While the expanded repertoire of β-oxidation auxiliary enzymes is considered crucial for Mtb adaptability, delineating their functional relevance has been challenging. Here, we show that the Mtb fatty acid degradation (FadAB) complex cannot selectively break down cis fatty acyl substrates. We demonstrate that the stereoselective binding of fatty acyl substrates in the Mtb FadB pocket is due to the steric hindrance from Phe287 residue. By developing a functional screen, we classify the family of Mtb Ech proteins as monofunctional or bifunctional enzymes, three of which complement the FadAB complex to degrade cis fatty acids. Crystal structure determination of two cis-trans enoyl coenzyme A (CoA) isomerases reveals distinct placement of active-site residue in Ech enzymes. Our studies thus reveal versatility of Mtb lipid-remodeling enzymes and identify an essential role of stand-alone cis-trans enoyl CoA isomerases in mycobacterial biology.