4GK8

Crystal structure of histidinol phosphate phosphatase (HISK) from Lactococcus lactis subsp. lactis Il1403 complexed with ZN and L-histidinol arsenate

Summary for 4GK8

• Entry DOI: 10.2210/pdb4gk8/pdb
• Related: 4GC3
• Descriptor: Histidinol-phosphatase, ZINC ION, {[(2S)-2-amino-3-(1H-imidazol-5-yl)propyl]oxy}(trihydroxy)-lambda~5~-arsanyl, ... (7 entities in total)
• Functional Keywords: php fold, hydrolase
• Biological source: Lactococcus lactis subsp. lactis
• Total number of polymer chains: 1
• Total formula weight: 34045.08

Authors

Fedorov, A.A.,Fedorov, E.V.,Ghodge, S.,Raushel, F.M.,Almo, S.C. (deposition date: 2012-08-10, release date: 2013-02-27, Last modification date: 2023-09-13)

Primary citation

Ghodge, S.V.,Fedorov, A.A.,Fedorov, E.V.,Hillerich, B.,Seidel, R.,Almo, S.C.,Raushel, F.M.
Structural and Mechanistic Characterization of l-Histidinol Phosphate Phosphatase from the Polymerase and Histidinol Phosphatase Family of Proteins.
Biochemistry, 52:1101-1112, 2013

PubMed Abstract: L-Histidinol phosphate phosphatase (HPP) catalyzes the hydrolysis of L-histidinol phosphate to L-histidinol and inorganic phosphate, the penultimate step in the biosynthesis of L-histidine. HPP from the polymerase and histidinol phosphatase (PHP) family of proteins possesses a trinuclear active site and a distorted (β/α)(7)-barrel protein fold. This group of enzymes is closely related to the amidohydrolase superfamily of enzymes. The mechanism of phosphomonoester bond hydrolysis by the PHP family of HPP enzymes was addressed. Recombinant HPP from Lactococcus lactis subsp. lactis that was expressed in Escherichia coli contained a mixture of iron and zinc in the active site and had a catalytic efficiency of ~10(3) M(-1) s(-1). Expression of the protein under iron-free conditions resulted in the production of an enzyme with a 2 order of magnitude improvement in catalytic efficiency and a mixture of zinc and manganese in the active site. Solvent isotope and viscosity effects demonstrated that proton transfer steps and product dissociation steps are not rate-limiting. X-ray structures of HPP were determined with sulfate, L-histidinol phosphate, and a complex of L-histidinol and arsenate bound in the active site. These crystal structures and the catalytic properties of variants were used to identify the structural elements required for catalysis and substrate recognition by the HPP family of enzymes within the amidohydrolase superfamily.

PubMed: 23327428
DOI: 10.1021/bi301496p

Experimental method

X-RAY DIFFRACTION (1.933 Å)