The Ternary Structure of the Double-headed Arrowhead Protease Inhibitor API-A Complexed with Two Trypsins Reveals a Novel Reactive Site Conformation
文献类型：期刊论文
| 作者 | Bao, R; Zhou, CZ; Jiang, CH; Lin, SX; Chi, CW; Chen, YX |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2009 |
| 卷号 | 284期号:39页码:26676-26684 |
| 通讯作者 | Chi, CW (reprint author), Tongji Univ, Inst Prot Res, Shanghai 200092, Peoples R China.,zwqi@sibs.ac.cn ; cyxing@ustc.edu.cn |
| 英文摘要 | The double-headed arrowhead protease inhibitors API-A and -B from the tubers of Sagittaria sagittifolia (Linn) feature two distinct reactive sites, unlike other members of their family. Although the two inhibitors have been extensively characterized, the identities of the two P1 residues in both API-A and -B remain controversial. The crystal structure of a ternary complex at 2.48 angstrom resolution revealed that the two trypsins bind on opposite sides of API-A and are 34 angstrom apart. The overall fold of API-A belongs to the beta-trefoil fold and resembles that of the soybean Kunitz-type trypsin inhibitors. The two P1 residues were unambiguously assigned as Leu(87) and Lys(145), and their identities were further confirmed by site-directed mutagenesis. Reactive site 1, composed of residues P5 Met(83) to P5' Ala(92), adopts a novel conformation with the Leu87 completely embedded in the S1 pocket even though it is an unfavorable P1 residue for trypsin. Reactive site 2, consisting of residues P5 Cys(141) to P5' Glu(150), binds trypsin in the classic mode by employing a two-disulfide-bonded loop. Analysis of the two binding interfaces sheds light on atomic details of the inhibitor specificity and also promises potential improvements in enzyme activity by engineering of the reactive sites. |
| 学科主题 | Biochemistry & Molecular Biology |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | BOWMAN-BIRK INHIBITOR ; 1.9 ANGSTROM RESOLUTION ; CRYSTAL-STRUCTURE ; PROTEINASE-INHIBITORS ; PORCINE TRYPSIN ; BOVINE TRYPSIN ; CHYMOTRYPSIN INHIBITOR ; PLASMINOGEN-ACTIVATOR ; ERYTHRINA-CAFFRA ; BARLEY-SEEDS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000269969600048 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1297]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Bao, R,Zhou, CZ,Jiang, CH,et al. The Ternary Structure of the Double-headed Arrowhead Protease Inhibitor API-A Complexed with Two Trypsins Reveals a Novel Reactive Site Conformation[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2009,284(39):26676-26684. |
| APA | Bao, R,Zhou, CZ,Jiang, CH,Lin, SX,Chi, CW,&Chen, YX.(2009).The Ternary Structure of the Double-headed Arrowhead Protease Inhibitor API-A Complexed with Two Trypsins Reveals a Novel Reactive Site Conformation.JOURNAL OF BIOLOGICAL CHEMISTRY,284(39),26676-26684. |
| MLA | Bao, R,et al."The Ternary Structure of the Double-headed Arrowhead Protease Inhibitor API-A Complexed with Two Trypsins Reveals a Novel Reactive Site Conformation".JOURNAL OF BIOLOGICAL CHEMISTRY 284.39(2009):26676-26684. |
入库方式： OAI收割
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。