5UDQ

LarE, a sulfur transferase involved in synthesis of the cofactor for lactate racemase, apo form

Summary for 5UDQ

• Entry DOI: 10.2210/pdb5udq/pdb
• Related: 5UDR 5UDS 5UDT 5UDU 5UDV 5UDW 5UDX
• Descriptor: Lactate racemization operon protein LarE, SULFATE ION, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: lar, sulfur transferase, lare, ampylation, hexamer, trimer, pp-loop, atp pyrophophatase domain, lactate, lactate racemization, lactate racemase, transferase
• Biological source: Lactobacillus plantarum (strain ATCC BAA-793 / NCIMB 8826 / WCFS1)
• Total number of polymer chains: 6
• Total formula weight: 191650.93

Authors

Fellner, M.,Desguin, B.,Hausinger, R.P.,Hu, J. (deposition date: 2016-12-28, release date: 2017-08-23, Last modification date: 2019-11-27)

Primary citation

Fellner, M.,Desguin, B.,Hausinger, R.P.,Hu, J.
Structural insights into the catalytic mechanism of a sacrificial sulfur insertase of the N-type ATP pyrophosphatase family, LarE.
Proc. Natl. Acad. Sci. U.S.A., 114:9074-9079, 2017

PubMed Abstract: The operon in encodes five Lar proteins (LarA/B/C/D/E) that collaboratively synthesize and incorporate a niacin-derived Ni-containing cofactor into LarA, an Ni-dependent lactate racemase. Previous studies have established that two molecules of LarE catalyze successive thiolation reactions by donating the sulfur atom of their exclusive cysteine residues to the substrate. However, the catalytic mechanism of this very unusual sulfur-sacrificing reaction remains elusive. In this work, we present the crystal structures of LarE in ligand-free and several ligand-bound forms, demonstrating that LarE is a member of the N-type ATP pyrophosphatase (PPase) family with a conserved N-terminal ATP PPase domain and a unique C-terminal domain harboring the putative catalytic site. Structural analysis, combined with structure-guided mutagenesis, leads us to propose a catalytic mechanism that establishes LarE as a paradigm for sulfur transfer through sacrificing its catalytic cysteine residue.

PubMed: 28784764
DOI: 10.1073/pnas.1704967114

Experimental method

X-RAY DIFFRACTION (2.09 Å)