Crystal structure of the proenzyme domain of plasminogen

被引：37

作者：

Peisach, E

Wang, JY

de los Santos, T

Reich, E

Ringe, D ^{[1
]}

机构：

[1] Brandeis Univ, Dept Biochem, Waltham, MA 02454 USA

[2] Brandeis Univ, Dept Chem, Waltham, MA 02254 USA

[3] Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02254 USA

[4] Brandeis Univ, Program Biophys & Struct Biol, Waltham, MA 02254 USA

[5] SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA

来源：

BIOCHEMISTRY | 1999年 / 38卷 / 34期

关键词：

D O I：

10.1021/bi991130r

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have solved the X-ray crystal structure of the proenzyme form of the catalytic domain of plasminogen, with the nonessential mutations M585Q, V673M, and M788L, to 2.0 Angstrom resolution. The structure presents an inactive protease characterized by Asp740 (chymotrypsinogen 194) hydrogen bonded to His586 (chymotrypsinogen 40), preventing proper formation of the oxyanion hole and SI specificity pocket. In addition, the catalytic triad residues are misplaced relative to the active conformation adopted by serine proteases in the chymotrypsin family. Finally, a unique form of zymogen inactivation is observed, characterized by a "foot-in-mouth" mechanism in which Trp761 (chymotrypsinogen 215) is folded into the S1 specificity pocket preventing substrate binding.

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收藏

页码：11180 / 11188

页数：9

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