1npm

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1npm, resolution 2.1Å

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NEUROPSIN, A SERINE PROTEASE EXPRESSED IN THE LIMBIC SYSTEM OF MOUSE BRAIN

Overview

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-gamma, (NGFgamma), 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 NGFgamma. 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.

About this Structure

1NPM is a Single protein structure of sequence from Mus musculus with NAG as ligand. Structure known Active Sites: ACA and ACB. Full crystallographic information is available from OCA.

Reference

Crystal structure of neuropsin, a hippocampal protease involved in kindling epileptogenesis., Kishi T, Kato M, Shimizu T, Kato K, Matsumoto K, Yoshida S, Shiosaka S, Hakoshima T, J Biol Chem. 1999 Feb 12;274(7):4220-4. PMID:9933620

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