PMID- 22172596
OWN - NLM
STAT- MEDLINE
DCOM- 20120604
LR  - 20220408
IS  - 1638-6183 (Electronic)
IS  - 0300-9084 (Linking)
VI  - 94
IP  - 3
DP  - 2012 Mar
TI  - Genetic and biochemical characterization of Corynebacterium glutamicum ATP 
      phosphoribosyltransferase and its three mutants resistant to feedback inhibition 
      by histidine.
PG  - 829-38
LID - 10.1016/j.biochi.2011.11.015 [doi]
AB  - ATP phosphoribosyltransferase (ATP-PRT) catalyzes the condensation of ATP and 
      PRPP at the first step of histidine biosynthesis and is regulated by a feedback 
      inhibition from product histidine. Here, we report the genetic and biochemical 
      characterization of such an enzyme, HisG(Cg), from Corynebacterium glutamicum, 
      including site-directed mutagenesis of the histidine-binding site for the first 
      time. Gene disruption and complementation experiments showed that HisG(Cg) is 
      essential for histidine biosynthesis. HisG(Cg) activity was noncompetitively 
      inhibited by histidine and the alpha-amino group of histidine were found to play an 
      important role for its binding to HisG(Cg). Homology-based modeling predicted 
      that four residues (N215, L231, T235 and A270) in the C-terminal domain of 
      HisG(Cg) may affect the histidine inhibition. Mutating these residues in HisG(Cg) 
      did not cause significant change in the specific activities of the enzyme but 
      resulted in the generation of mutant ones resistant to histidine inhibition. Our 
      data identified that the mutant N215K/L231F/T235A resists to histidine inhibition 
      the most with 37-fold increase in K(i) value. As expected, overexpressing a 
      hisG(Cg) gene containing N215K/L231F/T235A mutations in vivo promoted histidine 
      accumulation to a final concentration of 0.15 +/- 0.01 mM. Our results demonstrated 
      that the polarity change of electrostatic potential of mutant protein surface 
      prevents histidine from binding to the C-terminal domain of HisG(Cg), resulting 
      in the release of allosteric inhibition. Considering that these residues were 
      highly conserved in ATP-PRTs from different genera of Gram-positive bacteria the 
      mechanism by histidine inhibition as exhibited in Corynebacterium glutamicum 
      probably represents a ubiquitously inhibitory mechanism of ATP-PRTs by histidine.
CI  - Copyright (c) 2011 Elsevier Masson SAS. All rights reserved.
FAU - Zhang, Yun
AU  - Zhang Y
AD  - Department of Industrial Microbiology and Biotechnology, Institute of 
      Microbiology, Chinese Academy of Sciences, 100101 Beijing, China.
FAU - Shang, Xiuling
AU  - Shang X
FAU - Deng, Aihua
AU  - Deng A
FAU - Chai, Xin
AU  - Chai X
FAU - Lai, Shujuan
AU  - Lai S
FAU - Zhang, Guoqiang
AU  - Zhang G
FAU - Wen, Tingyi
AU  - Wen T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111208
PL  - France
TA  - Biochimie
JT  - Biochimie
JID - 1264604
RN  - 0 (Mutant Proteins)
RN  - 4QD397987E (Histidine)
RN  - EC 2.4.2.17 (ATP Phosphoribosyltransferase)
SB  - IM
MH  - ATP Phosphoribosyltransferase/genetics/*metabolism
MH  - Corynebacterium glutamicum/*enzymology
MH  - Histidine/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Mutant Proteins/genetics/*metabolism
EDAT- 2011/12/17 06:00
MHDA- 2012/06/05 06:00
CRDT- 2011/12/17 06:00
PHST- 2011/09/22 00:00 [received]
PHST- 2011/11/30 00:00 [accepted]
PHST- 2011/12/17 06:00 [entrez]
PHST- 2011/12/17 06:00 [pubmed]
PHST- 2012/06/05 06:00 [medline]
AID - S0300-9084(11)00454-8 [pii]
AID - 10.1016/j.biochi.2011.11.015 [doi]
PST - ppublish
SO  - Biochimie. 2012 Mar;94(3):829-38. doi: 10.1016/j.biochi.2011.11.015. Epub 2011 
      Dec 8.