PMID- 23700425
OWN - NLM
STAT- MEDLINE
DCOM- 20140218
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 5
DP  - 2013
TI  - Substrate specificity provides insights into the sugar donor recognition 
      mechanism of O-GlcNAc transferase (OGT).
PG  - e63452
LID - 10.1371/journal.pone.0063452 [doi]
LID - e63452
AB  - O-Linked beta-N-acetylglucosaminyl transferase (OGT) plays an important role in the 
      glycosylation of proteins, which is involved in various cellular events. In 
      human, three isoforms of OGT (short OGT [sOGT]; mitochondrial OGT [mOGT]; and 
      nucleocytoplasmic OGT [ncOGT]) share the same catalytic domain, implying that 
      they might adopt a similar catalytic mechanism, including sugar donor 
      recognition. In this work, the sugar-nucleotide tolerance of sOGT was 
      investigated. Among a series of uridine 5'-diphosphate-N-acetylglucosamine 
      (UDP-GlcNAc) analogs tested using the casein kinase II (CKII) peptide as the 
      sugar acceptor, four compounds could be used by sOGT, including 
      UDP-6-deoxy-GlcNAc, UDP-GlcNPr, UDP-6-deoxy-GalNAc and UDP-4-deoxy-GlcNAc. 
      Determined values of Km showed that the substitution of the N-acyl group, deoxy 
      modification of C6/C4-OH or epimerization of C4-OH of the GlcNAc in UDP-GlcNAc 
      decreased its affinity to sOGT. A molecular docking study combined with 
      site-directed mutagenesis indicated that the backbone carbonyl oxygen of Leu653 
      and the hydroxyl group of Thr560 in sOGT contributed to the recognition of the 
      sugar moiety via hydrogen bonds. The close vicinity between Met501 and the N-acyl 
      group of GlcNPr, as well as the hydrophobic environment near Met501, were 
      responsible for the selective binding of UDP-GlcNPr. These findings illustrate 
      the interaction of OGT and sugar nucleotide donor, providing insights into the 
      OGT catalytic mechanism.
FAU - Ma, Xiaofeng
AU  - Ma X
AD  - College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology and 
      Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 
      China.
FAU - Liu, Pi
AU  - Liu P
FAU - Yan, Hui
AU  - Yan H
FAU - Sun, Hong
AU  - Sun H
FAU - Liu, Xiaoyan
AU  - Liu X
FAU - Zhou, Feng
AU  - Zhou F
FAU - Li, Lei
AU  - Li L
FAU - Chen, Yi
AU  - Chen Y
FAU - Muthana, Musleh M
AU  - Muthana MM
FAU - Chen, Xi
AU  - Chen X
FAU - Wang, Peng G
AU  - Wang PG
FAU - Zhang, Lianwen
AU  - Zhang L
LA  - eng
GR  - R01 HD065122/HD/NICHD NIH HHS/United States
GR  - R01HD065122/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130521
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - EC 2.4.1.- (N-Acetylglucosaminyltransferases)
RN  - EC 2.4.1.- (O-GlcNAc transferase)
RN  - V956696549 (Acetylglucosamine)
SB  - IM
MH  - Acetylglucosamine/*analogs & derivatives/*chemistry
MH  - Amino Acid Substitution
MH  - Catalytic Domain
MH  - Humans
MH  - Hydrogen Bonding
MH  - Kinetics
MH  - Molecular Docking Simulation
MH  - Mutagenesis, Site-Directed
MH  - N-Acetylglucosaminyltransferases/*chemistry/genetics
MH  - Protein Binding
MH  - Substrate Specificity
PMC - PMC3660302
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/05/24 06:00
MHDA- 2014/02/19 06:00
PMCR- 2013/05/21
CRDT- 2013/05/24 06:00
PHST- 2013/01/05 00:00 [received]
PHST- 2013/04/02 00:00 [accepted]
PHST- 2013/05/24 06:00 [entrez]
PHST- 2013/05/24 06:00 [pubmed]
PHST- 2014/02/19 06:00 [medline]
PHST- 2013/05/21 00:00 [pmc-release]
AID - PONE-D-13-01074 [pii]
AID - 10.1371/journal.pone.0063452 [doi]
PST - epublish
SO  - PLoS One. 2013 May 21;8(5):e63452. doi: 10.1371/journal.pone.0063452. Print 2013.