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PDBsum entry 1l8k
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structure determination of t cell protein-Tyrosine phosphatase.
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Authors
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L.F.Iversen,
K.B.Moller,
A.K.Pedersen,
G.H.Peters,
A.S.Petersen,
H.S.Andersen,
S.Branner,
S.B.Mortensen,
N.P.Moller.
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Ref.
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J Biol Chem, 2002,
277,
19982-19990.
[DOI no: ]
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PubMed id
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Abstract
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Protein-tyrosine phosphatase 1B (PTP1B) has recently received much attention as
a potential drug target in type 2 diabetes. This has in particular been spurred
by the finding that PTP1B knockout mice show increased insulin sensitivity and
resistance to diet-induced obesity. Surprisingly, the highly homologous T cell
protein-tyrosine phosphatase (TC-PTP) has received much less attention, and no
x-ray structure has been provided. We have previously co-crystallized PTP1B with
a number of low molecular weight inhibitors that inhibit TC-PTP with similar
efficiency. Unexpectedly, we were not able to co-crystallize TC-PTP with the
same set of inhibitors. This seems to be due to a multimerization process where
residues 130-132, the DDQ loop, from one molecule is inserted into the active
site of the neighboring molecule, resulting in a continuous string of
interacting TC-PTP molecules. Importantly, despite the high degree of functional
and structural similarity between TC-PTP and PTP1B, we have been able to
identify areas close to the active site that might be addressed to develop
selective inhibitors of each enzyme.
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Figure 2.
Fig. 2. Chemical structures.
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Figure 6.
Fig. 6. Grasp rendering of the PTP1B and TC-PTP surfaces.
The two surface areas with structural differences useful for
potential selectivity design are indicated by white and yellow
circles, respectively. The surface electrostatic potentials are
colored in blue for positive charges and in red for negative
charges.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2002,
277,
19982-19990)
copyright 2002.
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