Serpin Inhibition Mechanism: A Delicate Balance between Native Metastable State and Polymerization

Table 4

Analysis of the residue burial and stability of natural variant of serpin involved in polymerization.

Serpins	ASA^b	ΔΔG^c
	(Native)	(kcal/mol)
Antithrombin-P80 S/T^a	0.0	−0.97, −0.72
Antithrombin-T85 M/K^a	2.9	−0.73, −3.04
Antithrombin-C95R	9.3	−1.33
Antithrombin-L99F	1.1	−1.03
Antithrombin-N187D	9.6	−1.92
Antithrombin-F229L	1.5	−0.92
Antithrombin-A382T	28.0	−0.33
Antithrombin-G424R	2.5	−1.30
Antithrombin-P429L	12.7	−0.18
Antitrypsin-F51L	0.0	−1.42
Antitrypsin-S53F	0.0	−0.42
Antitrypsin-V55P	2.6	−2.28
Antitrypsin-E264V	5.2	0.47
Antitrypsin-E342T	6.9	1.02
Neuroserpin-S49P	0.0	−1.19
Neuroserpin-S52R	0.0	−1.06
Neuroserpin-H338R	0.0	−1.37
Neuroserpin-G392E	0.0	−0.30
Antichymotrypsin-L55P	1.6	−2.17
Antichymotrypsin-P228A	4.9	−1.45
Heparin Cofactor-II-E428K	18.0	−0.22

^aTwo different variant at the same position.
^bAccessible Surface Area (ASA) values were determined from DSSP algorithm. The pdb codes used for the analysis are as follows: antithrombin (1t1f), antitrypsin (1qlp), neuroserpin (1jjo and 3fgq), antichymotrypsin (1yxa), and heparin cofactor-II (1jmj).
^cΔΔG were determined for the variants by using Imutant 2.0 at pH 7.0 and 25°C, the values were determined by using the difference of ΔG between the wild-type and the polymerization variants mentioned in the table.