1L7N

TRANSITION STATE ANALOGUE OF PHOSPHOSERINE PHOSPHATASE (ALUMINUM FLUORIDE COMPLEX)

Summary for 1L7N

• Entry DOI: 10.2210/pdb1l7n/pdb
• Related: 1F5S 1J97 1L7M 1L7O 1L7P
• Descriptor: PHOSPHOSERINE PHOSPHATASE, TETRAFLUOROALUMINATE ION, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: rossmann fold, b-hairpin, four-helix bundle, structural genomics, bsgc structure funded by nih, protein structure initiative, psi, berkeley structural genomics center, hydrolase
• Biological source: Methanocaldococcus jannaschii
• Total number of polymer chains: 2
• Total formula weight: 48069.27

Authors

Wang, W.,Cho, H.S.,Kim, R.,Jancarik, J.,Yokota, H.,Nguyen, H.H.,Grigoriev, I.V.,Wemmer, D.E.,Kim, S.H.,Berkeley Structural Genomics Center (BSGC) (deposition date: 2002-03-16, release date: 2002-06-19, Last modification date: 2024-10-30)

Primary citation

Wang, W.,Cho, H.S.,Kim, R.,Jancarik, J.,Yokota, H.,Nguyen, H.H.,Grigoriev, I.V.,Wemmer, D.E.,Kim, S.H.
Structural characterization of the reaction pathway in phosphoserine phosphatase: crystallographic "snapshots" of intermediate states.
J.Mol.Biol., 319:421-431, 2002

PubMed Abstract: Phosphoserine phosphatase (PSP) is a member of a large class of enzymes that catalyze phosphoester hydrolysis using a phosphoaspartate-enzyme intermediate. PSP is a likely regulator of the steady-state d-serine level in the brain, which is a critical co-agonist of the N-methyl-d-aspartate type of glutamate receptors. Here, we present high-resolution (1.5-1.9 A) structures of PSP from Methanococcus jannaschii, which define the open state prior to substrate binding, the complex with phosphoserine substrate bound (with a D to N mutation in the active site), and the complex with AlF3, a transition-state analog for the phospho-transfer steps in the reaction. These structures, together with those described for the BeF3- complex (mimicking the phospho-enzyme) and the enzyme with phosphate product in the active site, provide a detailed structural picture of the full reaction cycle. The structure of the apo state indicates partial unfolding of the enzyme to allow substrate binding, with refolding in the presence of substrate to provide specificity. Interdomain and active-site conformational changes are identified. The structure with the transition state analog bound indicates a "tight" intermediate. A striking structure homology, with significant sequence conservation, among PSP, P-type ATPases and response regulators suggests that the knowledge of the PSP reaction mechanism from the structures determined will provide insights into the reaction mechanisms of the other enzymes in this family.

PubMed: 12051918
DOI: 10.1016/S0022-2836(02)00324-8

Experimental method

X-RAY DIFFRACTION (1.8 Å)