5EQ8: Crystal Structure Of Medicago Truncatula Histidinol-phosphate Phosphatase (mthpp) In Complex With L-histidinol

The penultimate enzyme in the histidine biosynthetic pathway catalyzes dephosphorylation of l-histidinol 1-phosphate (HOLP) into l-histidinol. The recently discovered in Arabidopsis thaliana plant-type histidinol phosphate phosphatase (HPP) shares no homology with the two other HPP superfamilies known previously in prokaryotes and resembles myo-inositol monophosphatases (IMPases). In this work, identification of an HPP enzyme from a model legume, Medicago truncatula (MtHPP) was based on the highest sequence identity to A. thaliana enzyme. Biochemical assays confirmed that MtHPP was able to cleave inorganic phosphate from HOLP but not from d-myo-inositol-1-phosphate, the main substrate of IMPases. Dimers of MtHPP, determined by size exclusion chromatography, in the presence of CO2 or formaldehyde form mutual, methylene-bridged cross-links between Lys(158) and Cys(245) residues. Four high resolution crystal structures, namely complexes with HOLP (substrate), l-histidinol (product), and PO4 (3-) (by-product) as well as the structure showing the cross-linking between two MtHPP molecules, provide detailed structural information on the enzyme. Based on the crystal structures, the enzymatic reaction mechanism of IMPases is accustomed to fit the data for MtHPP. The enzymatic reaction, which requires Mg(2+) cations, is catalyzed mainly by amino acid residues from the N-terminal domain. The C-terminal domain, sharing little identity with IMPases, is responsible for the substrate specificity (i.e. allows the enzyme to distinguish between HOLP and d-myo-inositol-1-phosphate). Structural features, mainly the presence of a conserved Asp(246), allow MtHPP to bind HOLP specifically.
PDB ID: 5EQ8Download
MMDB ID: 137912
PDB Deposition Date: 2015/11/12
Updated in MMDB: 2016/06
Experimental Method:
x-ray diffraction
Resolution: 1.3  Å
Source Organism:
Similar Structures:
Biological Unit for 5EQ8: dimeric; determined by author and by software (PISA)
Molecular Components in 5EQ8
Label Count Molecule
Proteins (2 molecules)
Inositol Monophosphatase
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

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