4BX3
Crystal Structure of murine Chronophin (Pyridoxal Phosphate Phosphatase)
Summary for 4BX3
| Entry DOI | 10.2210/pdb4bx3/pdb |
| Related | 4BX0 4BX2 |
| Descriptor | PYRIDOXAL PHOSPHATE PHOSPHATASE, MAGNESIUM ION, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | hydrolase, pdxp, had phosphatase, had-like hydrolase |
| Biological source | MUS MUSCULUS (HOUSE MOUSE) |
| Cellular location | Cytoplasm, cytosol (By similarity): P60487 |
| Total number of polymer chains | 2 |
| Total formula weight | 63462.66 |
| Authors | Knobloch, G.,Gohla, A.,Schindelin, H. (deposition date: 2013-07-08, release date: 2013-12-25, Last modification date: 2024-11-20) |
| Primary citation | Kestler, C.,Knobloch, G.,Tessmer, I.,Jeanclos, E.,Schindelin, H.,Gohla, A. Chronophin Dimerization is Required for Proper Positioning of its Substrate Specificity Loop. J.Biol.Chem., 289:3094-, 2014 Cited by PubMed Abstract: Mammalian phosphatases of the haloacid dehalogenase (HAD) superfamily have emerged as important regulators of physiology and disease. Many of these enzymes are stable homodimers; however, the role of their dimerization is largely unknown. Here, we explore the function of the obligatory homodimerization of chronophin, a mammalian HAD phosphatase known to dephosphorylate pyridoxal 5'-phosphate (PLP) and serine/threonine-phosphorylated proteins. The exchange of two residues in the murine chronophin homodimerization interface (chronophin(A194K,A195K)) yields a constitutive monomer both in vitro and in cells. The catalytic activity of monomeric chronophin toward PLP is strongly impaired. X-ray crystallographic studies of chronophin(A194K,A195K) revealed that dimer formation is essential for an intermolecular arginine-arginine-tryptophan stacking interaction that positions a critical histidine residue in the substrate specificity loop of chronophin for PLP coordination. Analysis of all available crystal structures of HAD hydrolases that are grouped together with chronophin in the C2a-type structural subfamily uncovered a highly conserved mode of dimerization that results in intermolecular contacts involving the substrate specificity loop. Our results explain how the dimerization of HAD hydrolases contributes to their catalytic efficiency and substrate specificity. PubMed: 24338687DOI: 10.1074/JBC.M113.536482 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.193 Å) |
Structure validation
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