RT Journal Article
SR Electronic
T1 A complex iron-calcium cofactor catalyzing phosphotransfer chemistry
JF Science
JO Science
FD American Association for the Advancement of Science
SP 1170
OP 1173
DO 10.1126/science.1254237
VO 345
IS 6201
A1 Yong, Shee Chien
A1 Roversi, Pietro
A1 Lillington, James
A1 Rodriguez, Fernanda
A1 Krehenbrink, Martin
A1 Zeldin, Oliver B.
A1 Garman, Elspeth F.
A1 Lea, Susan M.
A1 Berks, Ben C.
YR 2014
UL http://science.sciencemag.org/content/345/6201/1170.abstract
AB Microbes require inventive ways to acquire scarce nutrients from the environment. Enzymes that catalyze the acquisition of phosphorus from dissolved organic matter, for example, rely on complex metal cofactors in the active site. Yong et al. determined the crystal structure of the PhoX alkaline phosphatase from Pseudomonas fluorescens (see the Perspective by Moore). The metal centers arrange themselves in a triangular structure of two iron atoms and one calcium atom, bridged together by an oxide ion. The presence of iron, which itself is a trace nutrient in most environments, suggests that it limits phosphorus acquisition.Science, this issue p. 1170; see also p. 1120 Alkaline phosphatases play a crucial role in phosphate acquisition by microorganisms. To expand our understanding of catalysis by this class of enzymes, we have determined the structure of the widely occurring microbial alkaline phosphatase PhoX. The enzyme contains a complex active-site cofactor comprising two antiferromagnetically coupled ferric iron ions (Fe3+), three calcium ions (Ca2+), and an oxo group bridging three of the metal ions. Notably, the main part of the cofactor resembles synthetic oxide-centered triangular metal complexes. Structures of PhoX-ligand complexes reveal how the active-site metal ions bind substrate and implicate the cofactor oxo group in the catalytic mechanism. The presence of iron in PhoX raises the possibility that iron bioavailability limits microbial phosphate acquisition.