1GJ5

SELECTIVITY AT S1, H2O DISPLACEMENT, UPA, TPA, SER190/ALA190 PROTEASE, STRUCTURE-BASED DRUG DESIGN

Summary for 1GJ5

• Entry DOI: 10.2210/pdb1gj5/pdb
• Related: 1C5N
• Descriptor: THROMBIN, ACETYL HIRUDIN, SODIUM ION, ... (6 entities in total)
• Functional Keywords: three-centered, very short hydrogen bond, oxyanion hole water, shift of pka of his57, structure-based drug design, specificity, urokinase, trypsin, thrombin, zn+2-mediated inhibition, blood clotting, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase-inhibitor complex, hydrolase/inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted, extracellular space: P00734 P00734; Secreted: P28504
• Total number of polymer chains: 3
• Total formula weight: 35590.52

Authors

Katz, B.A.,Sprengeler, P.A.,Luong, C.,Verner, E.,Spencer, J.R.,Breitenbucher, J.G.,Hui, H.,McGee, D.,Allen, D.,Martelli, A.,Mackman, R.L. (deposition date: 2001-04-27, release date: 2002-04-27, Last modification date: 2024-10-30)

Primary citation

Katz, B.A.,Sprengeler, P.A.,Luong, C.,Verner, E.,Elrod, K.,Kirtley, M.,Janc, J.,Spencer, J.R.,Breitenbucher, J.G.,Hui, H.,McGee, D.,Allen, D.,Martelli, A.,Mackman, R.L.
Engineering inhibitors highly selective for the S1 sites of Ser190 trypsin-like serine protease drug targets.
Chem.Biol., 8:1107-1121, 2001

PubMed Abstract: Involved or implicated in a wide spectrum of diseases, trypsin-like serine proteases comprise well studied drug targets and anti-targets that can be subdivided into two major classes. In one class there is a serine at position 190 at the S1 site, as in urokinase type plasminogen activator (urokinase or uPA) and factor VIIa, and in the other there is an alanine at 190, as in tissue type plasminogen activator (tPA) and factor Xa. A hydrogen bond unique to Ser190 protease-arylamidine complexes between O gamma(Ser190) and the inhibitor amidine confers an intrinsic preference for such inhibitors toward Ser190 proteases over Ala190 counterparts.

PubMed: 11731301
DOI: 10.1016/S1074-5521(01)00084-9

Experimental method

X-RAY DIFFRACTION (1.73 Å)