1GJ7

ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OF SER190 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS

Summary for 1GJ7

• Entry DOI: 10.2210/pdb1gj7/pdb
• Related: 1C5X
• Descriptor: UROKINASE-TYPE PLASMINOGEN ACTIVATOR, CITRIC ACID, 6-CHLORO-2-(2-HYDROXY-BIPHENYL-3-YL)-1H-INDOLE-5-CARBOXAMIDINE, ... (5 entities in total)
• Functional Keywords: selectivity at s1, h2o displacement, upa, tpa, ser190/ala190 protease, structure-based drug design, blood clotting, hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P00749 P00749
• Total number of polymer chains: 2
• Total formula weight: 31890.69

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 (1.5 Å)