1BJV

BETA-TRYPSIN COMPLEXED WITH APPU

1BJV の概要

• エントリーDOI: 10.2210/pdb1bjv/pdb
• 分子名称: BETA-TRYPSIN, CALCIUM ION, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: hydrolase, serine protease, digestion, pancreas, zymogen
• 由来する生物種: Bos taurus (cattle)
• 細胞内の位置: Secreted, extracellular space: P00760
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23981.01

構造登録者

Presnell, S.,Patil, G.,Mura, C.,Jude, K.,Conley, J.,Kam, C.,Bertrand, J.,Powers, J.,Williams, L. (登録日: 1998-06-29, 公開日: 1998-12-02, 最終更新日: 2024-11-20)

主引用文献

Presnell, S.R.,Patil, G.S.,Mura, C.,Jude, K.M.,Conley, J.M.,Bertrand, J.A.,Kam, C.M.,Powers, J.C.,Williams, L.D.
Oxyanion-mediated inhibition of serine proteases.
Biochemistry, 37:17068-17081, 1998

PubMed Abstract: Novel aryl derivatives of benzamidine were synthesized and tested for their inhibitory potency against bovine trypsin, rat skin tryptase, human recombinant granzyme A, human thrombin, and human plasma kallikrein. All compounds show competitive inhibition against these proteases with Ki values in the micromolar range. X-ray structures were determined to 1.8 A resolution for trypsin complexed with two of the para-substituted benzamidine derivatives, 1-(4-amidinophenyl)-3-(4-chlorophenyl)urea (ACPU) and 1-(4-amidinophenyl)-3-(4-phenoxyphenyl)urea (APPU). Although the inhibitors do not engage in direct and specific interactions outside the S1 pocket, they do form intimate indirect contacts with the active site of trypsin. The inhibitors are linked to the enzyme by a sulfate ion that forms an intricate network of three-centered hydrogen bonds. Comparison of these structures with other serine protease structures with noncovalently bound oxyanions reveals a pair of highly conserved oxyanion-binding sites in the active site. The positions of noncovalently bound oxyanions, such as the oxygen atoms of sulfate, are distinct from the positions of covalent oxyanions of tetrahedral intermediates. Noncovalent oxyanion positions are outside the "oxyanion hole." Kinetics data suggest that protonation stabilizes the ternary inhibitor/oxyanion/protease complex. In sum, both cations and anions can mediate Ki. Cation mediation of potency of competitive inhibitors of serine proteases was previously reported by Stroud and co-workers [Katz, B. A., Clark, J. M., Finer-Moore, J. S., Jenkins, T. E., Johnson, C. R., Ross, M. J., Luong, C., Moore, W. R., and Stroud, R. M. (1998) Nature 391, 608-612].

PubMed: 9836602
DOI: 10.1021/bi981636u

実験手法

X-RAY DIFFRACTION (1.8 Å)