PMID- 10427002
OWN - NLM
STAT- MEDLINE
DCOM- 19990816
LR  - 20190619
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 285
IP  - 5428
DP  - 1999 Jul 30
TI  - Two-metal-Ion catalysis in adenylyl cyclase.
PG  - 756-60
AB  - Adenylyl cyclase (AC) converts adenosine triphosphate (ATP) to cyclic adenosine
      monophosphate, a ubiquitous second messenger that regulates many cellular
      functions. Recent structural studies have revealed much about the structure and
      function of mammalian AC but have not fully defined its active site or catalytic 
      mechanism. Four crystal structures were determined of the catalytic domains of AC
      in complex with two different ATP analogs and various divalent metal ions. These 
      structures provide a model for the enzyme-substrate complex and conclusively
      demonstrate that two metal ions bind in the active site. The similarity of the
      active site of AC to those of DNA polymerases suggests that the enzymes catalyze 
      phosphoryl transfer by the same two-metal-ion mechanism and likely have evolved
      from a common ancestor.
FAU - Tesmer, J J
AU  - Tesmer JJ
AD  - Howard Hughes Medical Institute, Department of Biochemistry, University of Texas 
      Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9050,
      USA.
FAU - Sunahara, R K
AU  - Sunahara RK
FAU - Johnson, R A
AU  - Johnson RA
FAU - Gosselin, G
AU  - Gosselin G
FAU - Gilman, A G
AU  - Gilman AG
FAU - Sprang, S R
AU  - Sprang SR
LA  - eng
SI  - PDB/1CJK
SI  - PDB/1CJT
SI  - PDB/1CJU
SI  - PDB/1CJV
GR  - DK38828/DK/NIDDK NIH HHS/United States
GR  - DK46371/DK/NIDDK NIH HHS/United States
GR  - GM34497/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Adenylyl Cyclase Inhibitors)
RN  - 0 (Deoxyadenine Nucleotides)
RN  - 0 (Dideoxynucleotides)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Ligands)
RN  - 0 (Thionucleotides)
RN  - 0 (adenosine 5'-(1-thio)triphosphate)
RN  - 24027-80-3 (2',3'-dideoxyadenosine triphosphate)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - 42Z2K6ZL8P (Manganese)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
RN  - I38ZP9992A (Magnesium)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Adenylyl Cyclase Inhibitors
MH  - Adenylyl Cyclases/chemistry/genetics/*metabolism
MH  - Animals
MH  - Aspartic Acid/metabolism
MH  - Binding Sites
MH  - Catalysis
MH  - Crystallography, X-Ray
MH  - Deoxyadenine Nucleotides/metabolism/pharmacology
MH  - Dideoxynucleotides
MH  - Dimerization
MH  - Enzyme Inhibitors/metabolism
MH  - Hydrogen Bonding
MH  - Ligands
MH  - Magnesium/*metabolism
MH  - Manganese/*metabolism
MH  - Models, Molecular
MH  - Mutation
MH  - Protein Conformation
MH  - Protein Folding
MH  - Rats
MH  - Thionucleotides/metabolism/pharmacology
MH  - Zinc/*metabolism
EDAT- 1999/07/31 00:00
MHDA- 1999/07/31 00:01
CRDT- 1999/07/31 00:00
PHST- 1999/07/31 00:00 [pubmed]
PHST- 1999/07/31 00:01 [medline]
PHST- 1999/07/31 00:00 [entrez]
AID - 7687 [pii]
AID - 10.1126/science.285.5428.756 [doi]
PST - ppublish
SO  - Science. 1999 Jul 30;285(5428):756-60. doi: 10.1126/science.285.5428.756.