PMID- 11325033
OWN - NLM
STAT- MEDLINE
DCOM- 20010521
LR  - 20071114
IS  - 1085-9195 (Print)
IS  - 1085-9195 (Linking)
VI  - 33
IP  - 2
DP  - 2000
TI  - Structure and function of S-adenosylhomocysteine hydrolase.
PG  - 101-25
AB  - In mammals, S-adenosylhomocysteine hydrolase (AdoHcyase) is the only known enzyme 
      to catalyze the breakdown of S-adenosylhomocysteine (AdoHcy) to homocysteine and 
      adenosine. AdoHcy is the product of all adenosylmethionine (AdoMet)-dependent 
      biological transmethylations. These reactions have a wide range of products, and 
      are common in all facets of biometabolism. As a product inhibitor, elevated 
      levels of AdoHcy suppress AdoMet-dependent transmethylations. Thus, AdoHcyase is 
      a regulator of biological transmethylation in general. The three-dimensional 
      structure of AdoHcyase complexed with reduced nicotinamide adenine dinucleotide 
      phosphate (NADH) and the inhibitor (1'R, 2'S, 
      3'R)-9-(2',3'-dihyroxycyclopenten-1-yl)adenine (DHCeA) was solved by a 
      combination of the crystallographic direct methods program, SnB, to determine the 
      selenium atom substructure and by treating the multiwavelength anomalous 
      diffraction data as a special case of multiple isomorphous replacement. The 
      enzyme architecture resembles that observed for NAD-dependent dehydrogenases, 
      with the catalytic domain and the cofactor-binding domain each containing a 
      modified Rossmann fold. The two domains form a deep active site cleft containing 
      the cofactor and bound inhibitor molecule. A comparison of the inhibitor complex 
      of the human enzyme and the structure of the rat enzyme, solved without 
      inhibitor, suggests that a 17 degrees rigid body movement of the catalytic domain 
      occurs upon inhibitor/substrate binding.
FAU - Turner, M A
AU  - Turner MA
AD  - Structural Biology and Biochemistry, Hospital for Sick Children,Toronto, ON, 
      Canada.
FAU - Yang, X
AU  - Yang X
FAU - Yin, D
AU  - Yin D
FAU - Kuczera, K
AU  - Kuczera K
FAU - Borchardt, R T
AU  - Borchardt RT
FAU - Howell, P L
AU  - Howell PL
LA  - eng
GR  - GM 29332/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Cell Biochem Biophys
JT  - Cell biochemistry and biophysics
JID - 9701934
RN  - 0 (Antiparasitic Agents)
RN  - 0 (Antiviral Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - EC 3.- (Hydrolases)
RN  - EC 3.3.1.1 (Adenosylhomocysteinase)
SB  - IM
MH  - Adenosylhomocysteinase
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antiparasitic Agents/pharmacology
MH  - Antiviral Agents/pharmacology
MH  - Enzyme Inhibitors/chemistry/pharmacology
MH  - Humans
MH  - Hydrolases/*chemistry/drug effects/*metabolism
MH  - Mammals
MH  - Molecular Sequence Data
MH  - Protein Conformation
MH  - Protein Structure, Secondary
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
RF  - 107
EDAT- 2001/04/28 10:00
MHDA- 2001/05/25 10:01
CRDT- 2001/04/28 10:00
PHST- 2001/04/28 10:00 [pubmed]
PHST- 2001/05/25 10:01 [medline]
PHST- 2001/04/28 10:00 [entrez]
AID - CBB:33:2:101 [pii]
AID - 10.1385/CBB:33:2:101 [doi]
PST - ppublish
SO  - Cell Biochem Biophys. 2000;33(2):101-25. doi: 10.1385/CBB:33:2:101.