The catalytic cycle of P‐glycoprotein
Tóm tắt
P‐glycoprotein is a plasma‐membrane glycoprotein which confers multidrug‐resistance on cells and displays ATP‐driven drug‐pumping in vitro. It contains two nucleotide‐binding domains, and its structure places it in the ‘ABC transporter’ family. We review recent evidence that both nucleotide‐sites bind and hydrolyse Mg‐ATP. The two catalytic sites interact strongly. A minimal scheme for the MgATP hydrolysis reaction is presented. An alternating catalytic sites scheme is proposed, in which drug transport is coupled to relaxation of a high‐energy catalytic site conformation generated by the hydrolysis step. Other ABC transporters may show similar catalytic features.
Tài liệu tham khảo
10.1146/annurev.bi.58.070189.001033
10.1146/annurev.bi.62.070193.002125
Gros P., 1993, Int. Rev. Cytol., 137, 169, 10.1016/S0074-7696(08)62604-2
10.1007/BF02110325
Gottesman M.M., 1993, Cancer Res., 53, 747
Childs S., 1994, Important Advances in Oncology, 21
10.1016/1040-8428(92)90057-W
10.1146/annurev.cb.08.110192.000435
10.1016/0005-2736(73)90191-0
10.1016/0005-2736(74)90148-5
10.1016/S0021-9258(17)32712-6
10.1016/S0021-9258(20)80510-9
10.1007/BF02110326
10.1016/S0021-9258(18)47390-5
10.1016/S0021-9258(18)80120-X
10.1016/0014-5793(94)00447-1
10.1002/j.1460-2075.1982.tb01276.x
10.1016/S0021-9258(18)42909-2
10.1016/S0021-9258(18)53597-3
10.1016/S0021-9258(17)41923-5
10.1021/bi00189a008
10.1074/jbc.270.37.21449
10.1042/bj3080381
10.1038/316820a0
10.1016/S0021-9258(17)37065-5
10.1007/BF02110328
10.1016/0005-2736(93)90339-2
10.1006/abbi.1995.1020
10.1128/MCB.14.1.277
10.1016/0014-5793(93)80888-2
Bibi E., 1993, Proc. Natl. Acad. Sci. USA, 9209
10.1007/BF02110331
10.1021/bi00200a011
10.1074/jbc.270.19.11040
10.1016/S0021-9258(18)82708-9
10.1002/jcp.1041480321
10.1074/jbc.270.39.22957
10.1016/S0021-9258(17)37350-7
10.1128/MCB.9.12.5289
10.1074/jbc.270.33.19383
Urbatsch I.L., 1995, J. Biol. Chem., 270
10.1146/annurev.bi.52.070183.002115