4EGV

Crystal structure of a monomeric SCP2-thiolase like protein type 1 (STLP1) from Mycobacterium smegmatis

Summary for 4EGV

• Entry DOI: 10.2210/pdb4egv/pdb
• Descriptor: Acetyl-CoA acetyltransferase (2 entities in total)
• Functional Keywords: new sub-family, thiolase fold, transferase
• Biological source: Mycobacterium smegmatis
• Total number of polymer chains: 6
• Total formula weight: 337193.69

Authors

Janardan, N.,Harijan, R.K.,Wierenga, R.K.,Murthy, M.R.N. (deposition date: 2012-04-01, release date: 2012-09-12, Last modification date: 2024-11-20)

Primary citation

Janardan, N.,Harijan, R.K.,Wierenga, R.K.,Murthy, M.R.N.
Crystal Structure of a Monomeric Thiolase-Like Protein Type 1 (TLP1) from Mycobacterium smegmatis.
Plos One, 7:e41894-e41894, 2012

PubMed Abstract: An analysis of the Mycobacterium smegmatis genome suggests that it codes for several thiolases and thiolase-like proteins. Thiolases are an important family of enzymes that are involved in fatty acid metabolism. They occur as either dimers or tetramers. Thiolases catalyze the Claisen condensation of two acetyl-Coenzyme A molecules in the synthetic direction and the thiolytic cleavage of 3-ketoacyl-Coenzyme A molecules in the degradative direction. Some of the M. smegmatis genes have been annotated as thiolases of the poorly characterized SCP2-thiolase subfamily. The mammalian SCP2-thiolase consists of an N-terminal thiolase domain followed by an additional C-terminal domain called sterol carrier protein-2 or SCP2. The M. smegmatis protein selected in the present study, referred to here as the thiolase-like protein type 1 (MsTLP1), has been biochemically and structurally characterized. Unlike classical thiolases, MsTLP1 is a monomer in solution. Its structure has been determined at 2.7 Å resolution by the single wavelength anomalous dispersion method. The structure of the protomer confirms that the N-terminal domain has the thiolase fold. An extra C-terminal domain is indeed observed. Interestingly, it consists of six β-strands forming an anti-parallel β-barrel which is completely different from the expected SCP2-fold. Detailed sequence and structural comparisons with thiolases show that the residues known to be essential for catalysis are not conserved in MsTLP1. Consistent with this observation, activity measurements show that MsTLP1 does not catalyze the thiolase reaction. This is the first structural report of a monomeric thiolase-like protein from any organism. These studies show that MsTLP1 belongs to a new group of thiolase related proteins of unknown function.

PubMed: 22844533
DOI: 10.1371/journal.pone.0041894

Experimental method

X-RAY DIFFRACTION (2.71 Å)