Molecular Dynamics Simulation of the Inhibition Against Arginase Ι Catalyzed Reaction by L-Val

doi:10.7503/cjcu20160007

Abstract

Abstract:

Molecular dynamics simulation and mutation were used to get the influence at activity and kinetics of enzyme catalyzed reaction by L-Val on W-Arginase Ι and R-Arginase Ι. There is a big cavity C2 near the activity pocket of Arginase Ι. The result of molecular dynamics simulation shows that the mutation of Ile156Arg narrows the cavity volume of C2. The experimental result shows that influenced by L-Val the half maximal inhibitory concentration(IC₅₀) of R-Arginase Ι has been risen obviously, the IC₅₀ by 3.06 mmol/L rises to 6.26 mmol/L. Therefore, Arginase Ι does exist a regulatory site in C2 and L-Val can combine on this site to disturb the activity of Arginase Ι.

Key words: Arginase Ι, Molecular dynamics simulation, Mutation, Half maximal inhibitory concentration(IC50), Regulatory site, L-Val

CLC Number:

O641

TrendMD:

HUANG Yiling, GAO Xuefeng. Molecular Dynamics Simulation of the Inhibition Against Arginase Ι Catalyzed Reaction by L-Val[J]. Chem. J. Chinese Universities, 2016, 37(5): 928.

Figures/Tables 5

Fig.1 Three-dimensional structure of ArginaseⅠThe secondary structure of ArginaseⅠis shown by ribbon model, His141 is shown by tube model, Mn2+ is shown by two balls, the α-helix is H1-helix between C1 and C2.

Scheme 1 Catalytic reaction by Arginase Ⅰ

Fig.2 RMSD curve(A) and amino acid RMSD(B) of W-ArginaseⅠand R-ArginaseⅠ

Fig.3 Structure of W-Arginase Ⅰ and R-Arginase ⅠThe secondary structure of W-ArginaseⅠ and R-Arginase Ⅰ is shown by ribbon model, the 156I of W-Arginase Ⅰ is shown by tube model, the 156R of R-Arginase Ⅰ is shown by ball-stick model.

Fig.4 Relationship between the initial reaction rate and the concentration of L-Vala. W-Arginase Ⅰ; b. R-Arginase Ⅰ.

References 24

[1]	Wu G., Morris S. M., Biochem.J., 1998, 336, 1—17
[2]	Kenyon N. J., Bratt J. M., Linderholm A. L., Last M. S., Last J. A., Toxicol. Appl.Pharmacol., 2008, 230(3), 269—275
[3]	Wang W. W., Jenkinson C. P., Griscavage J. M., Kern R. M., Arabolos N. S., Byrns R. E., Cederbaum S. D., Ignarro L. J., Biochem. Biophys. Res.Commun., 1995, 210(3), 1009—1016
[4]	Wei L. H., Jacobs A. T., Morris S. M. Jr., Ignairo L. J., Am. J. Physiol. Cell Physiol., 2000, 279(1), C248—256
[5]	Herzfeld A., Raper S. M., Biochem.J., 1976, 153, 469—478
[6]	Morris S. M., Auuu. Rev.Nutr., 2002, 22, 87—105
[7]	Morris S. M., Bhamidipati D., Kepka-Lenhart D., Gene, 1997, 193, 157—161
[8]	Cama E., Colleluori D. M., Emig F. A., Shin H., Kim S. W., Kim N. N., Traish A. M., Ash D. E., Christianson D. W., Biochem.J., 2003, 42, 8445—8451
[9]	Christianson D. W., Acc Chem.Res., 2005, 38(3), 191—201
[10]	Durante W., Tulis D. A., Keswanil A. N., Wang H., Peyton K. J., Circulation, 2006, 114, 69
[11]	Peyton K. J., Ensenat D., Azam M. A., Keswani A. N., Kannan S., Liu X. M., Wang H., Tulis D. A., Durante W., Arteriosclerosis Thrombosis and VascularBiology, 2009, 29(4), 488—494
[12]	Morris S. M. Jr., VascularMedicine, 2005, 10(S1), S83—S87
[13]	Tong B. C., Barbul A., Mini Reviews in Medicinal Chemistry, 2004, 4(8), 823—832
[14]	Bao M. Z., Foreign Medical Sciences(Section of Endocrinology), 2002, 22(5), 276—279
[15]	Christopher R., Rajivnath V., Shetty T. K., The Indian Journal of Pediatrics, 1997, 64(2), 266—269
[16]	Grody W. W., Klein D., Dodson A. E., Kern R. M., Wissmann P. B., Goodman B. K., Bassand P., Marescau B., Kang S. S., Leonard J. V., American Journal of Human Genetics, 1992, 50, 1281—1290
[17]	Reczkowski, Characterization of the Kinetic and Catalyticmechanism of Rat Liver Arginase, Temple University, Philadelphia, 1991
[18]	Tieleman D. P., Sansom M. S. P., Berendsen H. J. C., Biophys., 1999, 76, 40—49
[19]	Berger O., Edholm O., Jahnig F., Biophys., 1997, 72, 2002—2013
[20]	Marrink S. J., Berger O., Tieleman P., Jahnig F., Biophys., 1998, 74, 931—943
[21]	Tieleman D. P., Berendsen H. J. C., Sansom M. S. P., Biophys., 1999, 76, 1757—1769
[22]	Berendsen H. J. C., Postma J. P. M., Dinola A., Haak J. R. J., Chem.Phys., 1984, 81, 3684—3690
[23]	Pethe S., Boucher J. L., Mansuy D., Inorg. Biochem.J., 2002, 88, 397—402
[24]	Custot J., Moali C., Brollo M., J. Am. Chem.Soc., 1997, 119(17), 4086—4087