Crystal structure of trehalose‐6‐phosphate phosphatase–related protein: Biochemical and biological implications

• Published in: Protein science Vol. 15; no. 7; pp. 1735 - 1744
• Main Authors: Rao, Krishnamurthy N., Kumaran, Desigan, Seetharaman, Jayaraman, Bonanno, Jeffrey B., Burley, Stephen K., Swaminathan, Subramanyam
• Format: Journal Article
• Language: English
• Published: Bristol Cold Spring Harbor Laboratory Press 01.07.2006
• Subjects: Binding Sites; crystallography; enzymes; Hydrolases; phosphatase; Phosphoric Monoester Hydrolases - chemistry; Protein Conformation; protein structures; Sequence Homology, Amino Acid; structural genomics; structure; structure/function studies; Thermoplasma - enzymology; Thermoplasma acidophilum
• ISSN: 0961-8368; 1469-896X
• DOI: 10.1110/ps.062096606

We report here the crystal structure of a trehalose‐6‐phosphate phosphatase–related protein (T6PP) from Thermoplasma acidophilum, TA1209, determined by the dual‐wavelength anomalous diffraction (DAD) method. T6PP is a member of the haloacid dehalogenase (HAD) superfamily with significant sequence homology with trehalose‐6‐phosphate phosphatase, phosphoserine phosphatase, P‐type ATPases and other members of the family. T6PP possesses a core domain of known α/β‐hydrolase fold, characteristic of the HAD family, and a cap domain, with a tertiary fold consisting of a four‐stranded β‐sheet with two α‐helices on one side of the sheet. An active‐site magnesium ion and a glycerol molecule bound at the interface between the two domains provide insight into the mode of substrate binding by T6PP. A trehalose‐6‐phosphate molecule modeled into a cage formed by the two domains makes favorable interactions with the protein molecule. We have confirmed that T6PP is a trehalose phosphatase from amino acid sequence, three‐dimensional structure, and biochemical assays.