2OZX

Solution structure of human phosphohistidine phosphatase 1 in phosphate free form

Summary for 2OZX

• Entry DOI: 10.2210/pdb2ozx/pdb
• Related: 2AI6 2OZW
• NMR Information: BMRB: 6625
• Descriptor: 14 kDa phosphohistidine phosphatase (1 entity in total)
• Functional Keywords: alpha/beta architecture, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (By similarity): Q9NRX4
• Total number of polymer chains: 1
• Total formula weight: 13851.52

Authors

Gong, W.,Cui, G.,Jin, C.,Xia, B. (deposition date: 2007-02-27, release date: 2008-03-25, Last modification date: 2024-05-29)

Primary citation

Gong, W.,Li, Y.,Cui, G.,Hu, J.,Fang, H.,Jin, C.,Xia, B.
Solution structure and catalytic mechanism of human protein histidine phosphatase 1.
Biochem.J., 418:337-344, 2009

PubMed Abstract: Protein histidine phosphorylation exists widely in vertebrates, and it plays important roles in signal transduction and other cellular functions. However, knowledge about eukaryotic PHPT (protein histidine phosphatase) is still very limited. To date, only one vertebrate PHPT has been discovered, and two crystal structures of hPHPT1 (human PHPT1) have been solved. However, these two structures gave different ligand-binding sites and co-ordination patterns. In the present paper, we have solved the solution structures of hPHPT1 in both P(i)-free and P(i)-bound states. Through comparison of the structures, along with a mutagenesis study, we have determined the active site of hPHPT1. In contrast with previous results, our results indicate that the active site is located between helix alpha1 and loop L5. His(53) was identified to be the catalytic residue, and the NH groups of residues His(53), Ala(54) and Ala(96) and the OH group of Ser(94) should act as anchors of P(i) or substrate by forming H-bonds with P(i). On the basis of our results, a catalytic mechanism is proposed for hPHPT1: the imidazole ring of His(53) serves as a general base to activate a water molecule, and the activated water would attack the substrate as a nucleophile in the catalysis; the positively charged side chain of Lys(21) can help stabilize the transition state. No similar catalytic mechanism can be found in the EzCatDB database.

PubMed: 18991813
DOI: 10.1042/BJ20081571

Experimental method

SOLUTION NMR