1UTO

Trypsin specificity as elucidated by LIE calculations, X-ray structures and association constant measurements

1UTO の概要

• エントリーDOI: 10.2210/pdb1uto/pdb
• 関連するPDBエントリー: 1AQ7 1AUJ 1AZ8 1BJU 1BJV 1BTP 1BTW 1BTX 1BTY 1BTZ 1C1N 1C1O 1C1P 1C1Q 1C1R 1C1S 1C1T 1C2D 1C2E 1C2F 1C2G 1C2H 1C2I 1C2J 1C2K 1C2L 1C2M 1C5P 1C5Q 1C5R 1C5S 1C5T 1C5U 1C5V 1C9T 1CE5 1CU7 1CU8 1CU9 1D6R 1EB2 1EJM 1EZX 1F0T 1F0U 1F2S 1G36 1G3B 1G3C 1G3D 1G3E 1G9I 1GBT 1GHZ 1GI0 1GI1 1GI2 1GI3 1GI4 1GI5 1GI6 1GJ6 1HJ9 1J8A 1JIR 1JRS 1JRT 1K1I 1K1J 1K1L 1K1M 1K1N 1K1O 1K1P 1LQE 1MAX 1MAY 1MTS 1MTU 1MTV 1MTW 1N6X 1N6Y 1NC6 1NTP 1O2H 1O2I 1O2J 1O2K 1O2L 1O2M 1O2N 1O2O 1O2P 1O2Q 1O2R 1O2S 1O2T 1O2U 1O2V 1O2W 1O2X 1O2Y 1O2Z 1O30 1O31 1O32 1O33 1O34 1O35 1O36 1O37 1O38 1O39 1O3A 1O3B 1O3C 1O3D 1O3E 1O3F 1O3G 1O3H 1O3I 1O3J 1O3K 1O3L 1O3M 1O3N 1O3O 1OPH 1OYQ 1PPC 1PPE 1PPH 1QA0 1QB1 1QB6 1QB9 1QBN 1QBO 1QCP 1QL7 1QL8 1SBW 1SFI 1SMF 1TAB 1TAW 1TGB 1TGC 1TGN 1TGS 1TGT 1TIO 1TLD 1TNG 1TNH 1TNI 1TNJ 1TNK 1TNL 1TPA 1TPO 1TPP 1TPS 1TYN 1UTN 1XUF 1XUG 1XUH 1XUI 1XUJ 1XUK 1YYY 1ZZZ 2BTC 2BZA 2PTC 2PTN 2TGA 2TGD 2TGP 2TGT 2TIO 2TLD 2TPI 3BTD 3BTE 3BTF 3BTG 3BTH 3BTK 3BTM 3BTQ 3BTT 3BTW 3PTB 3PTN 3TPI 4TPI 5PTP
• 分子名称: TRYPSINOGEN, 2-PHENYLETHYLAMINE, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: hydrolase, trypsin, inhibitor specificity, electrostatic interactions, cold-adaptation, molecular dynamics, binding free energy
• 由来する生物種: BOS TAURUS (BOVINE)
• 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: 25699.08

構造登録者

Leiros, H.-K.S.,Brandsdal, B.O.,Andersen, O.A.,Os, V.,Leiros, I.,Helland, R.,Otlewski, J.,Willassen, N.P.,Smalas, A.O. (登録日: 2003-12-09, 公開日: 2004-01-15, 最終更新日: 2011-07-13)

主引用文献

Leiros, H.-K.S.,Brandsdal, B.O.,Andersen, O.A.,Os, V.,Leiros, I.,Helland, R.,Otlewski, J.,Willassen, N.P.,Smalas, A.O.
Trypsin Specificity as Elucidated by Lie Calculations, X-Ray Structures, and Association Constant Measurements
Protein Sci., 13:1056-, 2004

PubMed Abstract: The variation in inhibitor specificity for five different amine inhibitors bound to CST, BT, and the cold-adapted AST has been studied by use of association constant measurements, structural analysis of high-resolution crystal structures, and the LIE method. Experimental data show that AST binds the 1BZA and 2BEA inhibitors 0.8 and 0.5 kcal/mole more strongly than BT. However, structural interactions and orientations of the inhibitors within the S1 site have been found to be virtually identical in the three enzymes studied. For example, the four water molecules in the inhibitor-free structures of AST and BT are channeled into similar positions in the S1 site, and the nitrogen atom(s) of the inhibitors are found in two cationic binding sites denoted Position1 and Position2. The hydrophobic binding contributions for all five inhibitors, estimated by the LIE calculations, are also in the same order (-2.1 +/- 0.2 kcal/mole) for all three enzymes. Our hypothesis is therefore that the observed variation in inhibitor binding arises from different electrostatic interactions originating from residues outside the S1 site. This is well illustrated by AST, in which Asp 150 and Glu 221B, despite some distance from the S1 binding site, lower the electrostatic potential of the S1 site and thus enhance substrate binding. Because the trends in the experimentally determined binding energies were reproduced by the LIE calculations after adding the contribution from long-range interactions, we find this method very suitable for rational studies of protein-substrate interactions.

PubMed: 15044735
DOI: 10.1110/PS.03498604

実験手法

X-RAY DIFFRACTION (1.15 Å)