2FS9

Human beta tryptase II with inhibitor CRA-28427

Summary for 2FS9

• Entry DOI: 10.2210/pdb2fs9/pdb
• Related: 2FS8
• Descriptor: Tryptase beta-2, ETHYL {(1S)-5-AMINO-1-[(5-{4-[(2,3-DIHYDRO-1H-INDEN-2-YLAMINO)CARBONYL]BENZYL}-1,2,4-OXADIAZOL-3-YL)CARBONYL]PENTYL}CARBAMATE (3 entities in total)
• Functional Keywords: serine protease, serine proteinase, 28427, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P20231
• Total number of polymer chains: 4
• Total formula weight: 112044.07

Authors

Somoza, J.R. (deposition date: 2006-01-21, release date: 2006-03-07, Last modification date: 2024-10-16)

Primary citation

McGrath, M.E.,Sprengeler, P.A.,Hirschbein, B.,Somoza, J.R.,Lehoux, I.,Janc, J.W.,Gjerstad, E.,Graupe, M.,Estiarte, A.,Venkataramani, C.,Liu, Y.,Yee, R.,Ho, J.D.,Green, M.J.,Lee, C.-S.,Liu, L.,Tai, V.,Spencer, J.,Sperandio, D.,Katz, B.A.
Structure-guided design of Peptide-based tryptase inhibitors.
Biochemistry, 45:5964-5973, 2006

PubMed Abstract: Improved peptide-based inhibitors of human beta tryptase were discovered using information gleaned from tripeptide library screening and structure-guided design methods, including fragment screening. Our efforts sought to improve this class of inhibitors by replacing the traditional Lys or Arg P1 element. The optimized compounds display low nanomolar potency against the mast cell target and several hundred-fold selectivity with respect to serine protease off targets. Thus, replacement of Lys/Arg at P1 in a peptide-like scaffold does not need to be accompanied by a loss in target affinity.

PubMed: 16681368
DOI: 10.1021/bi060173m

Experimental method

X-RAY DIFFRACTION (2.3 Å)