PMID- 19770507
OWN - NLM
STAT- MEDLINE
DCOM- 20100126
LR  - 20240408
IS  - 1399-0047 (Electronic)
IS  - 0907-4449 (Print)
IS  - 0907-4449 (Linking)
VI  - 65
IP  - Pt 10
DP  - 2009 Oct
TI  - Structure of D-alanine-D-alanine ligase from Thermus thermophilus HB8: cumulative 
      conformational change and enzyme-ligand interactions.
PG  - 1098-106
LID - 10.1107/S0907444909029710 [doi]
AB  - D-Alanine-D-alanine ligase (Ddl) is one of the key enzymes in peptidoglycan 
      biosynthesis and is an important target for drug discovery. The enzyme catalyzes 
      the condensation of two D-Ala molecules using ATP to produce D-Ala-D-Ala, which 
      is the terminal peptide of a peptidoglycan monomer. The structures of five forms 
      of the enzyme from Thermus thermophilus HB8 (TtDdl) were determined: unliganded 
      TtDdl (2.3 A resolution), TtDdl-adenylyl imidodiphosphate (2.6 A), TtDdl-ADP (2.2 
      A), TtDdl-ADP-D-Ala (1.9 A) and TtDdl-ATP-D-Ala-D-Ala (2.3 A). The central domain 
      rotates as a rigid body towards the active site in a cumulative manner in concert 
      with the local conformational change of three flexible loops depending upon 
      substrate or product binding, resulting in an overall structural change from the 
      open to the closed form through semi-open and semi-closed forms. 
      Reaction-intermediate models were simulated using TtDdl-complex structures and 
      other Ddl structures previously determined by X-ray methods. The catalytic 
      process accompanied by the cumulative conformational change has been elucidated 
      based on the intermediate models in order to provide new insights regarding the 
      details of the catalytic mechanism.
FAU - Kitamura, Yoshiaki
AU  - Kitamura Y
AD  - Riken SPring-8 Center, Harima Institute, Sayo, Hyogo 679-5148, Japan.
FAU - Ebihara, Akio
AU  - Ebihara A
FAU - Agari, Yoshihiro
AU  - Agari Y
FAU - Shinkai, Akeo
AU  - Shinkai A
FAU - Hirotsu, Ken
AU  - Hirotsu K
FAU - Kuramitsu, Seiki
AU  - Kuramitsu S
LA  - eng
SI  - PDB/2YZG
SI  - PDB/2YZN
SI  - PDB/2ZDG
SI  - PDB/2ZDH
SI  - PDB/2ZDQ
SI  - PDB/R2YZGSF
SI  - PDB/R2YZNSF
SI  - PDB/R2ZDGSF
SI  - PDB/R2ZDQSF
PT  - Journal Article
DEP - 20090916
PL  - United States
TA  - Acta Crystallogr D Biol Crystallogr
JT  - Acta crystallographica. Section D, Biological crystallography
JID - 9305878
RN  - 0 (Ligands)
RN  - EC 6.3.2.- (Peptide Synthases)
RN  - EC 6.3.2.4 (D-alanylalanine synthetase)
SB  - IM
MH  - Catalytic Domain
MH  - Crystallography, X-Ray
MH  - Ligands
MH  - Models, Molecular
MH  - Peptide Synthases/*chemistry
MH  - Protein Conformation
MH  - Thermus thermophilus/*enzymology
PMC - PMC2756165
EDAT- 2009/09/23 06:00
MHDA- 2010/01/27 06:00
PMCR- 2010/10/01
CRDT- 2009/09/23 06:00
PHST- 2009/06/22 00:00 [received]
PHST- 2009/07/27 00:00 [accepted]
PHST- 2009/09/23 06:00 [entrez]
PHST- 2009/09/23 06:00 [pubmed]
PHST- 2010/01/27 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - S0907444909029710 [pii]
AID - hm5077 [pii]
AID - 10.1107/S0907444909029710 [doi]
PST - ppublish
SO  - Acta Crystallogr D Biol Crystallogr. 2009 Oct;65(Pt 10):1098-106. doi: 
      10.1107/S0907444909029710. Epub 2009 Sep 16.