PMID- 20971157
OWN - NLM
STAT- MEDLINE
DCOM- 20110420
LR  - 20131121
IS  - 1638-6183 (Electronic)
IS  - 0300-9084 (Linking)
VI  - 93
IP  - 2
DP  - 2011 Feb
TI  - Functional and structural evaluation of cysteine residues in the human arsenic 
      (+3 oxidation state) methyltransferase (hAS3MT).
PG  - 369-75
LID - 10.1016/j.biochi.2010.10.010 [doi]
AB  - Arsenic (+3 oxidation state) methyltransferase (AS3MT) catalyzes the methylation 
      of inorganic arsenic (iAs) and plays important role in the detoxication of this 
      metalloid. There are fourteen cysteine residues in the human AS3MT (hAS3MT), 
      among which twelve are absolutely conserved; Cys334 and Cys360 are unique; Cys368 
      and Cys369 are identified as a CysCys pair. The roles of several conserved 
      cysteine residues in rat AS3MT and hAS3MT have been reported. Herein, the other 
      conserved cysteine residues (Cys72, Cys271, Cys375) and the unique ones (Cys334, 
      Cys360) were systematically replaced by serine using site-directed mutagenesis to 
      study their functions. The mutants were investigated for enzymatic activity, 
      kinetics, thermal stability and secondary structures. Present results indicate 
      that C72S is completely inactive in methylation of iAs and has distinct changes 
      in the secondary structures; Cys72 might form a critical intramolecular disulfide 
      bond with Cys250; Cys271 and Cys375 do not affect the activity and structure of 
      the hAS3MT. However, the mutations of Cys334 and Cys360 can decrease the 
      enzymatic turnovers and change the conformation of the hAS3MT. The kinetic data 
      show that Cys271, Cys334, Cys360 and Cys375 are not involved in the SAM binding. 
      Additionally, all these cysteine residues except Cys375 affect the thermotropic 
      properties of the hAS3MT.
CI  - Copyright A(c) 2010 Elsevier Masson SAS. All rights reserved.
FAU - Song, Xiaoli
AU  - Song X
AD  - State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical 
      Engineering, Nanjing University, Hankou Road 22, Nanjing 210093, PR China.
FAU - Geng, Zhirong
AU  - Geng Z
FAU - Li, Xiangli
AU  - Li X
FAU - Zhao, Qun
AU  - Zhao Q
FAU - Hu, Xin
AU  - Hu X
FAU - Zhang, Xinrong
AU  - Zhang X
FAU - Wang, Zhilin
AU  - Wang Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101030
PL  - France
TA  - Biochimie
JT  - Biochimie
JID - 1264604
RN  - 0 (Arsenites)
RN  - 7LP2MPO46S (S-Adenosylmethionine)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 2.1.1.137 (AS3MT protein, human)
RN  - K848JZ4886 (Cysteine)
RN  - N5509X556J (arsenite)
SB  - IM
MH  - Arsenites/metabolism
MH  - Biocatalysis
MH  - *Cysteine
MH  - Hot Temperature
MH  - Humans
MH  - Kinetics
MH  - Methyltransferases/*chemistry/genetics/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Mutation
MH  - Protein Structure, Secondary
MH  - S-Adenosylmethionine/metabolism
EDAT- 2010/10/26 06:00
MHDA- 2011/04/22 06:00
CRDT- 2010/10/26 06:00
PHST- 2010/07/14 00:00 [received]
PHST- 2010/10/14 00:00 [accepted]
PHST- 2010/10/26 06:00 [entrez]
PHST- 2010/10/26 06:00 [pubmed]
PHST- 2011/04/22 06:00 [medline]
AID - S0300-9084(10)00370-6 [pii]
AID - 10.1016/j.biochi.2010.10.010 [doi]
PST - ppublish
SO  - Biochimie. 2011 Feb;93(2):369-75. doi: 10.1016/j.biochi.2010.10.010. Epub 2010 
      Oct 30.