PMID- 10218106
OWN - NLM
STAT- MEDLINE
DCOM- 19990610
LR  - 20150521
IS  - 0065-258X (Print)
IS  - 0065-258X (Linking)
VI  - 73
DP  - 1999
TI  - Adenylosuccinate synthetase: recent developments.
PG  - 57-102, ix-x
AB  - By exerting strategic control on purine nucleotide biosynthesis, and by engaging 
      GTP-dependent transphosphorylation of IMP to activate loss of an oxygen atom
      during catalysis, adenylosuccinate synthetase remains as enzyme that justifiably 
      fascinates students of enzyme catalysis. This review describes how the balanced
      application of X-ray crystallography and enzyme kinetics has advanced the
      comprehension of the catalytic and regulatory properties of adenylosuccinate
      synthetase. Detailed analysis has demonstrated the formation of 6-phosphoryl-IMP,
      an intermediate originally postulated over 40 years ago on the basis of oxygen-18
      exchange experiments showing that position-6 oxygen of IMP becomes incorporated
      into phosphate. Inferences about the participation of amino acid side-chains that
      stabilize 6-P-IMP during catalysis have also been confirmed by site-directed
      mutagenesis and examination of such mutations on various kinetic parameters.
      Moreover, the action of certain regulatory ligands have also been viewed at
      atomic level resolution. For example, magnesium ion and GDP can induce
      conformational changes linked to the stabilization of one of two known
      conformations of the so-called 40s loop. Another significant finding is that two 
      magnesium ions play fundamental roles: one binding with high affinity to the
      substrate GTP, and a second binding with lower affinity to the co-substrate
      aspartate. These structural and kinetic studies have also formed the basis for
      clarifying the action of various inhibitors and potentially important
      pharmacologic agents with this key regulatory enzyme. Finally, this review
      explores the current status of investigations on gene structure and gene
      expression in a number of organisms.
FAU - Honzatko, R B
AU  - Honzatko RB
AD  - Department of Biochemistry and Biophysics, Iowa State University, Ames 50011,
      USA.
FAU - Stayton, M M
AU  - Stayton MM
FAU - Fromm, H J
AU  - Fromm HJ
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Adv Enzymol Relat Areas Mol Biol
JT  - Advances in enzymology and related areas of molecular biology
JID - 0337243
RN  - 0 (Ligands)
RN  - 0 (Recombinant Proteins)
RN  - EC 6.3.4.4 (Adenylosuccinate Synthase)
SB  - IM
MH  - Adenylosuccinate Synthase/chemistry/*genetics/*metabolism
MH  - Animals
MH  - Binding Sites
MH  - Humans
MH  - Kinetics
MH  - Ligands
MH  - Mice
MH  - Models, Molecular
MH  - Mutagenesis, Site-Directed
MH  - Protein Conformation
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Substrate Specificity
RF  - 131
EDAT- 1999/04/28 00:00
MHDA- 1999/04/28 00:01
CRDT- 1999/04/28 00:00
PHST- 1999/04/28 00:00 [pubmed]
PHST- 1999/04/28 00:01 [medline]
PHST- 1999/04/28 00:00 [entrez]
PST - ppublish
SO  - Adv Enzymol Relat Areas Mol Biol. 1999;73:57-102, ix-x.