Inhibition of human napsin A

被引：3

作者：

Cronshaw, RF

Schauer-Vukasinovic, V

Powell, DJ

Giller, T

Bur, D

Kay, J

机构：

[1] Univ Wales Coll Cardiff, Sch Biosci, Cardiff CF10 3US, S Glam, Wales

[2] F Hoffmann La Roche Ltd, CH-4070 Basel, Switzerland

[3] Glaxo SmithKline, Harlow CM19 5AD, Essex, England

来源：

PROTEIN AND PEPTIDE LETTERS | 2003年 / 10卷 / 01期

关键词：

new human aspartic proteinase; selectivity of inhibition; active site mapping; importance of S1/S3;

D O I：

10.2174/0929866033408237

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The newly-discovered human aspartic proteinase, napsin A was not susceptible to protein inhibitors from potato, squash or yeast but was weakly inhibited by the 17 kDa polypeptide from Ascaris lumbricoides and potently by isovaleryl and lactoyl-pepstatins. A series of synthetic inhibitors was also investigated which contained in the P-1-P-1' positions the dipeptide analogue statine or its phenylalanine or cyclohexylalanine homologues and in which the residues occupying P-4-P-3' were varied systematically. On this basis, the active site of napsin A can be readily distinguished from other human aspartic proteinases.

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收藏

页码：35 / 42

页数：8

相关论文

共 18 条

[1] CRYSTAL-STRUCTURES OF NATIVE AND INHIBITED FORMS OF HUMAN CATHEPSIN-D - IMPLICATIONS FOR LYSOSOMAL TARGETING AND DRUG DESIGN [J].

BALDWIN, ET ;

BHAT, TN ;

GULNIK, S ;

HOSUR, MV ;

SOWDER, RC ;

CACHAU, RE ;

COLLINS, J ;

SILVA, AM ;

ERICKSON, JW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (14) :6796-6800

[2]

BARRETT AJ, 1998, HDB PROTEOLYTIC ENZY, P802

[3] Aspartic proteinase inhibitors from tomato and potato are more potent against yeast proteinase A than cathepsin D [J].

Cater, SA ;

Lees, WE ;

Hill, J ;

Brzin, J ;

Kay, J ;

Phylip, LH .

BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 2002, 1596 (01) :76-82

[4] Purification, characterization and cloning of an aspartic proteinase inhibitor from squash phloem exudate [J].

Christeller, JT ;

Farley, PC ;

Ramsay, RJ ;

Sullivan, PA ;

Laing, WA .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1998, 254 (01) :160-167

[5] Napsin A, a member of the aspartic protease family, is abundantly expressed in normal lung and kidney tissue and is expressed in lung adenocarcinomas [J].

Chuman, Y ;

Bergman, AC ;

Ueno, T ;

Saito, S ;

Sakaguchi, K ;

Alaiya, AA ;

Franzén, B ;

Bergman, T ;

Arnott, D ;

Auer, G ;

Appella, E ;

Jörnvall, H ;

Linder, S .

FEBS LETTERS, 1999, 462 (1-2) :129-134

[6] Pronapsin A and B gene expression in normal and malignant human lung and mononuclear blood cells [J].

Cook, M ;

Bühling, F ;

Ansorge, S ;

Tatnell, PJ ;

Kay, J .

BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 2002, 1577 (01) :10-16

[7] X-ray structures of five renin inhibitors bound to saccharopepsin: Exploration of active-site specificity [J].

Cronin, NB ;

Badasso, MO ;

Tickle, IJ ;

Dreyer, T ;

Hoover, DJ ;

Rosati, RL ;

Humblet, CC ;

Lunney, EA ;

Cooper, JB .

JOURNAL OF MOLECULAR BIOLOGY, 2000, 303 (05) :745-760

[8] The two sides of enzyme-substrate specificity: lessons from the aspartic proteinases [J].

Dunn, BM ;

Hung, SH .

BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 2000, 1477 (1-2) :231-240

[9] Substrate and inhibitor profile of BACE (β-secretase) and comparison with other mammalian aspartic proteases [J].

Grüninger-Leitch, F ;

Schlatter, D ;

Küng, E ;

Nelböck, P ;

Döbeli, H .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (07) :4687-4693

[10] Identification of a novel aspartic protease (Asp 2) as β-secretase [J].

Hussain, I ;

Powell, D ;

Howlett, DR ;

Tew, DG ;

Week, TD ;

Chapman, C ;

Gloger, IS ;

Murphy, KE ;

Southan, CD ;

Ryan, DM ;

Smith, TS ;

Simmons, DL ;

Walsh, FS ;

Dingwall, C ;

Christie, G .

MOLECULAR AND CELLULAR NEUROSCIENCE, 1999, 14 (06) :419-427