PDBsum entry 4zrc

Transferase

PDB id: 4zrc

Contents

Protein chains

391 a.a.

Waters ×103

PDB id:

4zrc

Name:

Transferase

Title:

Crystal structure of msm-13, a putative t1-like thiolase from mycobacterium smegmatis

Structure:

Beta-ketothiolase. Chain: a, b, c, d. Engineered: yes

Source:

Mycobacterium smegmatis str. Mc2 155. Organism_taxid: 246196. Strain: mc2 155. Gene: msmeg_2207. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.70Å R-factor: 0.226 R-free: 0.283

Authors:

N.Janardan,R.K.Harijan,T.R.Keima,R.Wierenga,M.R.N.Murthy

Key ref:

N.Janardan et al. (2015). Structural characterization of a mitochondrial 3-ketoacyl-CoA (T1)-like thiolase from Mycobacterium smegmatis. Acta Crystallogr D Biol Crystallogr, 71, 2479-2493. PubMed id: 26627655 DOI: 10.1107/S1399004715019331

Date:

12-May-15 Release date: 18-May-16

Protein chains

A0QUH3  (A0QUH3_MYCS2) -  Probable acetyl-CoA acetyltransferase from Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155)

Seq: 407 a.a.

Struc: 391 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1107/S1399004715019331

Acta Crystallogr D Biol Crystallogr 71:2479-2493 (2015)

PubMed id: 26627655

Structural characterization of a mitochondrial 3-ketoacyl-CoA (T1)-like thiolase from Mycobacterium smegmatis.

N.Janardan, R.K.Harijan, T.R.Kiema, R.K.Wierenga, M.R.Murthy.

ABSTRACT

Thiolases catalyze the degradation and synthesis of 3-ketoacyl-CoA molecules. Here, the crystal structures of a T1-like thiolase (MSM-13 thiolase) from Mycobacterium smegmatis in apo and liganded forms are described. Systematic comparisons of six crystallographically independent unliganded MSM-13 thiolase tetramers (dimers of tight dimers) from three different crystal forms revealed that the two tight dimers are connected to a rigid tetramerization domain via flexible hinge regions, generating an asymmetric tetramer. In the liganded structure, CoA is bound to those subunits that are rotated towards the tip of the tetramerization loop of the opposing dimer, suggesting that this loop is important for substrate binding. The hinge regions responsible for this rotation occur near Val123 and Arg149. The Lα1-covering loop-Lα2 region, together with the Nβ2-Nα2 loop of the adjacent subunit, defines a specificity pocket that is larger and more polar than those of other tetrameric thiolases, suggesting that MSM-13 thiolase has a distinct substrate specificity. Consistent with this finding, only residual activity was detected with acetoacetyl-CoA as the substrate in the degradative direction. No activity was observed with acetyl-CoA in the synthetic direction. Structural comparisons with other well characterized thiolases suggest that MSM-13 thiolase is probably a degradative thiolase that is specific for 3-ketoacyl-CoA molecules with polar, bulky acyl chains.