TY - JOUR
T1 - Crystal structure of neuropsin, a hippocampal protease involved in kindling epileptogenesis
AU - Kishi, Tadaaki
AU - Kato, Masato
AU - Shimizu, Toshiyuki
AU - Kato, Keiko
AU - Matsumoto, Kazumasa
AU - Yoshida, Shigetaka
AU - Shiosaka, Sadao
AU - Hakoshima, Toshio
PY - 1999/2/12
Y1 - 1999/2/12
N2 - Neuropsin is a novel serine protease, the expression of which is highly localized in the limbic areas of the mouse brain and which is suggested to be involved in kindling epileptogenesis and hippocampal plasticity. The 2.1-A resolution crystal structure of neuropsin provides the first three- dimensional view of one of the serine proteases highly expressed in the nervous system, and reveals a serine protease fold that exhibits chimeric features between trypsin and nerve growth factor-γ (NGFγ), a member of the kallikrein family. Neuropsin possesses an N-glycosylated 'kallikrein loop' but forms six disulfide bonds corresponding to those of trypsin. The ordered kallikrein loop projects proline toward the active site to restrict smaller residues or proline at the P2 position of substrates. Loop F, which participates in forming the S3/S4 sites, is similar to trypsin rather than NGFγ. The unique conformations of loops G and H form an S1 pocket specific for both arginine and lysine. These characteristic loop structures forming the substrate-binding site suggest the novel substrate specificity of neuropsin and give a clue to the design of its specific inhibitors.
AB - Neuropsin is a novel serine protease, the expression of which is highly localized in the limbic areas of the mouse brain and which is suggested to be involved in kindling epileptogenesis and hippocampal plasticity. The 2.1-A resolution crystal structure of neuropsin provides the first three- dimensional view of one of the serine proteases highly expressed in the nervous system, and reveals a serine protease fold that exhibits chimeric features between trypsin and nerve growth factor-γ (NGFγ), a member of the kallikrein family. Neuropsin possesses an N-glycosylated 'kallikrein loop' but forms six disulfide bonds corresponding to those of trypsin. The ordered kallikrein loop projects proline toward the active site to restrict smaller residues or proline at the P2 position of substrates. Loop F, which participates in forming the S3/S4 sites, is similar to trypsin rather than NGFγ. The unique conformations of loops G and H form an S1 pocket specific for both arginine and lysine. These characteristic loop structures forming the substrate-binding site suggest the novel substrate specificity of neuropsin and give a clue to the design of its specific inhibitors.
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U2 - 10.1074/jbc.274.7.4220
DO - 10.1074/jbc.274.7.4220
M3 - Article
C2 - 9933620
AN - SCOPUS:0033548087
SN - 0021-9258
VL - 274
SP - 4220
EP - 4224
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 7
ER -