ABCMdb

PMID: 12391288

Gruol DJ, King MN, Kuehne ME
Evidence for the locations of distinct steroid and Vinca alkaloid interaction domains within the murine mdr1b P-glycoprotein.
Mol Pharmacol. 2002 Nov;62(5):1238-48., [PubMed]

Sentences

No. Mutations Sentence Comment

117 ABCB1 p.Ala301Thr ABCB1 p.Ala301Val ABCB1 p.Ala301Asp The A301D mutation occurs in the same residue as the A301T and A301V mutations. Login to comment 119 ABCB1 p.Ala229Val It contains two closely spaced mutations, A229V and W231L. Login to comment 127 ABCB1 p.Ala229Val In total, the process identified five new mutations, two of which (A229V, S308L) involve amino acids that had not been previously identified as contributing to steroid interactions with the P-gp. Login to comment 131 ABCB1 p.Ala301Asp ABCB1 p.Ala229Val The percentage of normalized change in resistance (N.C.R) is defined by the equation: N.C.R ϭ 100% ϫ (VAR IC50 - MS23IC50 )/(MS23 IC50 - W7TB IC50) Cell Line Vincristine Daunomycin Dexamethasone Puromycin Colchicine Mutation MSPD-10 N.C. ` ``` `` `` W231C MSPT-7 `` ``` ``` ``` ` A229V, W231L MSPD-60 `` N.C. ``` `` `` A301D MSMP-1 ` `` `` `` ``` S308L MSAC-52 ` N.C. `` N.C. ϩϩϩϩ L338F N.C., no change; ϩϩϩϩ, NCR increase Ն200%; `, NCR decrease Ն33%; ``, Ն67%; ```, Ն100%. Login to comment 153 ABCB1 p.Ala301Asp Daunomycin was used to evaluate the effect of the A301D mutation, expressed in the MSPD-60 cells, on the inhibitory activity of 5betaPodo. Login to comment 169 ABCB1 p.Trp232Cys In the human protein, the comparable mutation is W232C. Login to comment 172 ABCB1 p.Leu339Cys However, the human L339C mutation produced a nearly complete loss of the ability of methanethiosulfonate-verapamil to induce ATPase activity. Login to comment 179 ABCB1 p.Ser228Thr The most pronounced effect was caused by the S228T mutation expressed in the MSPP-21 cells. Login to comment 204 ABCB1 p.Ala301Val The mutation expressed in the MSPP-4 cells (A301V) shows the largest reduction of MEK-417 inhibitory activity. Login to comment 206 ABCB1 p.Ala301Val Thus, it seems unlikely that the (A301V) mutation interferes with the initial binding of Vinca alkaloids with the protein. Login to comment 207 ABCB1 p.Ala301Val It is possible that A301V promotes the transport of MEK-417 also, which would lead to lower inhibitory activity. Login to comment 298 ABCB1 p.Ala301Thr ABCB1 p.Ala301Val ABCB1 p.Ala301Asp Multiple mutations were also found at the A301 residue (A301V, A301T, A301D), although much less frequently than the changes at W231. Login to comment