 |
PDBsum entry 2b3h
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Structural basis for the functional differences between type i and type ii human methionine aminopeptidases.
|
|
|
Authors
|
|
A.Addlagatta,
X.Hu,
J.O.Liu,
B.W.Matthews.
|
|
|
Ref.
|
|
Biochemistry, 2005,
44,
14741-14749.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Determination of the crystal structure of human MetAP1 makes it possible, for
the first time, to compare the structures of a Type I and a Type II methionine
aminopeptidase (MetAP) from the same organism. Comparison of the Type I enzyme
with the previously reported complex of ovalicin with Type II MetAP shows that
the active site of the former is reduced in size and would incur steric clashes
with the bound inhibitor. This explains why ovalicin and related
anti-angiogenesis inhibitors target Type II human MetAP but not Type I. The
differences in both size and shape of the active sites between MetAP1 and MetAP2
also help to explain their different substrate specificity. In the presence of
excess Co(2+), a third cobalt ion binds in the active site region, explaining
why metal ions in excess can be inhibitory. Also, the N-terminal region of the
protein contains three distinct Pro-x-x-Pro motifs, supporting the prior
suggestion that this region of the protein may participate in binding to the
ribosome.
|
|
|
|
|
|
|
