1Z12

Crystal Structure of Bovine Low Molecular Weight PTPase Complexed with Vanadate

Summary for 1Z12

• Entry DOI: 10.2210/pdb1z12/pdb
• Related: 1DG9 1Z13 3PNT
• Descriptor: Low molecular weight phosphotyrosine protein phosphatase, VANADATE ION (2 entities in total)
• Functional Keywords: ptpase, vanadate complex, hydrolase
• Biological source: Bos taurus (cattle)
• Cellular location: Cytoplasm: P11064
• Total number of polymer chains: 1
• Total formula weight: 18061.26

Authors

Zhang, M.,Zhou, M.,Van Etten, R.L.,Stauffacher, C.V. (deposition date: 2005-03-03, release date: 2005-04-05, Last modification date: 2023-08-23)

Primary citation

Zhang, M.,Zhou, M.,Van Etten, R.L.,Stauffacher, C.V.
Crystal Structure of Bovine Low Molecular Weight Phosphotyrosyl Phosphatase Complexed with the Transition State Analog Vanadate
Biochemistry, 36:15-23, 1997

PubMed Abstract: The early transition metal oxoanions vanadate, molybdate, and tungstate are widely used inhibitors for phosphatase enzymes. These oxoanions could inhibit such enzymes by simply mimicking the tetrahedral geometry of phosphate ion. However, in some cases, the enzyme-inhibitor dissociation constants (Ki) for these oxoanions are much lower than that for phosphate. Such observations gave rise to the hypothesis that in some cases these transition metal oxoanions may inhibit phosphomonoesterases by forming complexes that resemble the trigonal bipyramidal geometry of the SN2(P) transition state. As a test of this, the crystal structures of a low molecular weight protein tyrosine phosphatase at pH 7.5 complexed with the inhibitors vanadate and molybdate were solved at 2.2 A resolution and compared to a newly refined 1.9 A structure of the enzyme. Geometric restraints on the oxoanions were relaxed during refinement in order to minimize model bias. Both inhibitors were bound at the active site, and the overall protein structures were left unchanged, although some small but significant side chain movements at the active site were observed. Vanadate ion formed a covalent linkage with the nucleophile Cys12 at the active site and exhibited a trigonal bipyramidal geometry. In contrast, simple tetrahedral geometry was observed for the weaker molybdate complex. These studies are consistent with the conclusion that vanadate inhibits tyrosine phosphatases by acting as a transition state analog. The structure of the vanadate complex may be expected to closely resemble the transition state for reactions catalyzed by protein tyrosine phosphatases.

PubMed: 8993313
DOI: 10.1021/bi961804n

Experimental method

X-RAY DIFFRACTION (2.2 Å)