2AYW

Crystal Structure of the complex formed between trypsin and a designed synthetic highly potent inhibitor in the presence of benzamidine at 0.97 A resolution

Summary for 2AYW

• Entry DOI: 10.2210/pdb2ayw/pdb
• Descriptor: Cationic trypsin, CALCIUM ION, 2-[2-({[4-(DIAMINOMETHYL)PHENYL]AMINO}CARBONYL)-6-METHOXYPYRIDIN-3-YL]-5-{[(1-FORMYL-2,2-DIMETHYLPROPYL)AMINO]CARBONYL}BENZOIC ACID, ... (7 entities in total)
• Functional Keywords: trypsin, benzamidine, inhibitor, hydrolase
• Biological source: Bos taurus (cattle)
• Cellular location: Secreted, extracellular space: P00760
• Total number of polymer chains: 1
• Total formula weight: 24839.00

Authors

Sherawat, M.,Kaur, P.,Perbandt, M.,Betzel, C.,Slusarchyk, W.A.,Bisacchi, G.S.,Chang, C.,Jacobson, B.L.,Einspahr, H.M.,Singh, T.P. (deposition date: 2005-09-09, release date: 2006-01-17, Last modification date: 2023-10-25)

Primary citation

Sherawat, M.,Kaur, P.,Perbandt, M.,Betzel, C.,Slusarchyk, W.A.,Bisacchi, G.S.,Chang, C.,Jacobson, B.L.,Einspahr, H.M.,Singh, T.P.
Structure of the complex of trypsin with a highly potent synthetic inhibitor at 0.97 A resolution.
Acta Crystallogr.,Sect.D, 63:500-507, 2007

PubMed Abstract: The structure of the complex formed between bovine beta-trypsin and the highly potent synthetic inhibitor 2-{3'-[5'-methoxy-2'-(N-p-diaminomethylphenyl)amido]-1'-pyrido}-5-(N-2''-t-butylethanol)amidobenzoic acid (C(28)H(32)N(5)O(6)) has been determined at 0.97 A resolution. X-ray intensity data were collected to 0.97 A under cryocooled conditions. The structure was refined anisotropically using REFMAC5 and SHELX-97 to R(cryst) factors of 13.4 and 12.6% and R(free) factors of 15.7 and 16.3%, respectively. Several regions of the main chain and side chains that have not been previously observed were clearly defined in the present structure. H atoms are indicated as significant peaks in an |F(o) - F(c)| difference map, which accounts for an estimated 35% of all H atoms at the 2.5sigma level. The C, N and O atoms are definitively differentiated in the electron-density maps. The amido part of the inhibitor occupies the specificity pocket and the remainder fills the remaining part of the ligand-binding cleft and interacts with the enzyme through an extensive network of hydrogen bonds. The inhibitor distorts the stereochemistry of the catalytic triad, Ser195-His57-Asp102, thereby blocking the proton-relay process of the active site by preventing the formation of the crucial hydrogen bond between His57 N(delta1) and Asp102 O(delta1).

PubMed: 17372355
DOI: 10.1107/S090744490700697X

Experimental method

X-RAY DIFFRACTION (0.97 Å)