PDBsum entry 2hc1

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Hydrolase PDB id
Protein chain
290 a.a.
_CL ×2
Waters ×362

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Key reference
Title Engineering the catalytic domain of human protein tyrosine phosphatase beta for structure-Based drug discovery.
Authors A.G.Evdokimov, M.Pokross, R.Walter, M.Mekel, B.Cox, C.Li, R.Bechard, F.Genbauffe, R.Andrews, C.Diven, B.Howard, V.Rastogi, J.Gray, M.Maier, K.G.Peters.
Ref. Acta Crystallogr D Biol Crystallogr, 2006, 62, 1435-1445. [DOI no: 10.1107/S0907444906037784]
PubMed id 17139078
Protein tyrosine phosphatases (PTPs) play roles in many biological processes and are considered to be important targets for drug discovery. As inhibitor development has proven challenging, crystal structure-based design will be very helpful to advance inhibitor potency and selectivity. Successful application of protein crystallography to drug discovery heavily relies on high-quality crystal structures of the protein of interest complexed with pharmaceutically interesting ligands. It is very important to be able to produce protein-ligand crystals rapidly and reproducibly for as many ligands as necessary. This study details our efforts to engineer the catalytic domain of human protein tyrosine phosphatase beta (HPTPbeta-CD) with properties suitable for rapid-turnaround crystallography. Structures of apo HPTPbeta-CD and its complexes with several novel small-molecule inhibitors are presented here for the first time.
Figure 3.
Figure 3 Detailed view of the PTP -CD active site. (a) Hydrogen-bonding network (blue dashes) bridging the ligand (vanadate ion, balls-and-stick representation) and the protein (sticks). (b) Side view depicting additional interactions (magenta dashes) between the ligand and polar residues in the active site. The partial covalent bond between Cys1904 and the V atom is shown as an orange dashed line. (c) Side view of a pTyr mimetic (p-ethyl phenylsulfamic acid) bound in the active site of the enzyme. Relevant hydrogen bonds are shown as colored dashes.
Figure 4.
Figure 4 Transition of the WPD-loop between open (light brown) and closed (green) states. The ligand (sulfamic acid, yellow) is shown in ball-and-stick representation and relevant protein residues are shown as sticks colored according to the loop state. The catalytically important water molecule is shown as a red sphere.
The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2006, 62, 1435-1445) copyright 2006.
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