Crystal Structure of a Periplasmic Substrate-Binding Protein in Complex with Calcium Lactate

Lactate is utilized in many biological processes, and its transport across biological membranes is mediated with various types of transporters. Here, we report the crystal structures of a lactate-binding protein of a TRAP (tripartite ATP-independent periplasmic) secondary transporter from Thermus thermophilus HB8. The folding of the protein is typical for a type 11 periplasmic solute-binding protein and forms a dimer in a back-to-back manner. One molecule Of L-lactate is clearly identified in a cleft of the protein as a complex with a calcium ion. Detailed crystallographic and biochemical analyses revealed that the calcium ion can be removed from the protein and replaced with other divalent cations. This characterization of the structure of a protein binding with calcium lactate makes a significant contribution to our understanding of the mechanisms by which calcium and lactate are accommodated in cells. (C) 2009 Elsevier Ltd. All rights reserved.