4BX2: Crystal Structure of murine Chronophin (Pyridoxal Phosphate Phosphatase) in complex with Beryllium trifluoride

Citation:
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.
PDB ID: 4BX2Download
MMDB ID: 116196
PDB Deposition Date: 2013/7/8
Updated in MMDB: 2013/12
Experimental Method:
x-ray diffraction
Resolution: 2.193  Å
Source Organism:
Similar Structures:
Biological Unit for 4BX2: dimeric; determined by author and by software (PISA)
Molecular Components in 4BX2
Label Count Molecule
Proteins (2 molecules)
2
Pyridoxal Phosphate Phosphatase(Gene symbol: Pdxp)
Molecule annotation
Chemicals (7 molecules)
1
2
2
2
3
3
* Click molecule labels to explore molecular sequence information.

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