5E0N

Crystal Structure of MSMEG_3139, a monofunctional enoyl CoA isomerase from M.smegmatis

Summary for 5E0N

• Entry DOI: 10.2210/pdb5e0n/pdb
• Descriptor: Enoyl-CoA hydratase/isomerase (2 entities in total)
• Functional Keywords: isomerase, fatty acid oxidation, crotonase superfamily
• Biological source: Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)
• Total number of polymer chains: 1
• Total formula weight: 31672.19

Authors

Priyadarshan, K.,Haque, A.S.,Anandakrishnan, M.,Sankaranarayanan, R. (deposition date: 2015-09-29, release date: 2016-02-03, Last modification date: 2023-11-08)

Primary citation

Srivastava, S.,Chaudhary, S.,Thukral, L.,Shi, C.,Gupta, R.D.,Gupta, R.,Priyadarshan, K.,Vats, A.,Haque, A.S.,Sankaranarayanan, R.,Natarajan, V.T.,Sharma, R.,Aldrich, C.C.,Gokhale, R.S.
Unsaturated Lipid Assimilation by Mycobacteria Requires Auxiliary cis-trans Enoyl CoA Isomerase.
Chem.Biol., 22:1577-1587, 2015

PubMed 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.

PubMed: 26628360
DOI: 10.1016/j.chembiol.2015.10.009

Experimental method

X-RAY DIFFRACTION (2.061 Å)