In molecular biology, adenylosuccinate synthase (or adenylosuccinate synthetase) (EC 6.3.4.4) is an enzyme that plays an important role in purine biosynthesis, by catalysing the guanosine triphosphate (GTP)-dependent conversion of inosine monophosphate (IMP) and aspartic acid to guanosine diphosphate (GDP), phosphate and N(6)-(1,2-dicarboxyethyl)-AMP. Adenylosuccinate synthetase has been characterised from various sources ranging from Escherichia coli (gene purA) to vertebrate tissues. In vertebrates, two isozymes are present: one involved in purine biosynthesis and the other in the purine nucleotide cycle.

Structure

The crystal structure of adenylosuccinate synthetase from E. coli reveals that the dominant structural element of each monomer of the homodimer is a central beta-sheet of 10 strands. The first nine strands of the sheet are mutually parallel with right-handed crossover connections between the strands. The 10th strand is antiparallel with respect to the first nine strands. In addition, the enzyme has two antiparallel beta-sheets, composed of two strands and three strands each, 11 alpha-helices and two short 3₁₀-helices. Further, it has been suggested that the similarities in the GTP-binding domains of the synthetase and the p21ras protein are an example of convergent evolution of two distinct families of GTP-binding proteins.^[1] Structures of adenylosuccinate synthetase from Triticum aestivum and Arabidopsis thaliana when compared with the known structures from E. coli reveals that the overall fold is very similar to that of the E. coli protein.^[2]

Isozymes

Humans express two adenylosuccinate synthase isozymes:

adenylosuccinate synthase

Identifiers

Symbol

ADSS

Other data

Chr. 1 q44

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Structures	Swiss-model
Domains	InterPro

adenylosuccinate synthase like 1

Identifiers

Symbol

Other data

Chr. 14 q32.33

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Structures	Swiss-model
Domains	InterPro

External links

References

^ Poland BW, Silva MM, Serra MA, Cho Y, Kim KH, Harris EM, Honzatko RB (December 1993). "Crystal structure of adenylosuccinate synthetase from Escherichia coli. Evidence for convergent evolution of GTP-binding domains". J. Biol. Chem. 268 (34): 25334–42. doi:10.1016/S0021-9258(19)74396-8. PMID 8244965.
^ Prade L, Cowan-Jacob SW, Chemla P, Potter S, Ward E, Fonne-Pfister R (February 2000). "Structures of adenylosuccinate synthetase from Triticum aestivum and Arabidopsis thaliana". J. Mol. Biol. 296 (2): 569–77. doi:10.1006/jmbi.1999.3473. PMID 10669609.

This article incorporates text from the public domain Pfam and InterPro: IPR001114

Purine metabolism

Anabolism

R5P→IMP:	Ribose-phosphate diphosphokinase Amidophosphoribosyltransferase Phosphoribosylglycinamide formyltransferase AIR synthetase (FGAM cyclase) Phosphoribosylaminoimidazole carboxylase Phosphoribosylaminoimidazolesuccinocarboxamide synthase IMP synthase
IMP→AMP:	Adenylosuccinate synthase Adenylosuccinate lyase reverse AMP deaminase
IMP→GMP:	IMP dehydrogenase GMP synthase reverse GMP reductase

Nucleotide salvage

Catabolism

Pyrimidine metabolism

Anabolism

CAD Carbamoyl phosphate synthase II Aspartate carbamoyltransferase Dihydroorotase
Dihydroorotate dehydrogenase Orotidine 5'-phosphate decarboxylase/Uridine monophosphate synthetase
CTP synthetase

Catabolism

Deoxyribonucleotides

v t e Enzymes: CO CS and CN ligases (EC 6.1-6.3)
6.1: Carbon-Oxygen	Aminoacyl tRNA synthetase Alanine Arginine Asparagine Aspartate Cysteine D-alanine—poly(phosphoribitol) ligase Glutamate Glutamine Glycine Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Proline Serine Threonine Tryptophan Tyrosine Valine
6.2: Carbon-Sulfur	Succinyl coenzyme A synthetase Acetyl—CoA synthetase Long-chain-fatty-acid—CoA ligase
6.3: Carbon-Nitrogen	Glutamine synthetase Ubiquitin ligase Cullin Von Hippel–Lindau tumor suppressor UBE3A Mdm2 Anaphase-promoting complex UBR1 Glutathione synthetase CTP synthetase Adenylosuccinate synthase Argininosuccinate synthase Holocarboxylase synthetase GMP synthase Asparagine synthetase Carbamoyl phosphate synthetase I II Glutamate–cysteine ligase

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)