The crystal structure of 5'-deoxy-5'-methylthioadenosine phosphorylase II from Sulfolobus solfataricus, a thermophilic enzyme stabilized by intramolecular disulfide bonds.
The crystal structure of Sulfolobus solfataricus 5'-deoxy-5'-methylthioadenosine phosphorylase II (SsMTAPII) in complex with 5'-deoxy-5'-methylthioadenosine (MTA) and sulfate was determined to 1.45A resolution. The hexameric structure of SsMTAPII is a dimer-of-trimers with one active site per monomer. The oligomeric assembly of the trimer and the monomer topology of SsMTAPII are almost identical with trimeric human 5'-deoxy-5'-methylthioadenosine phosphorylase (hMTAP). SsMTAPII is the first reported hexameric member in the trimeric class of purine nucleoside phosphorylase (PNP) from Archaea. Unlike hMTAP, which is highly specific for MTA, SsMTAPII also accepts adenosine as a substrate. The residues at the active sites of SsMTAPII and hMTAP are almost identical. The broad substrate specificity of SsMTAPII may be due to the flexibility of the C-terminal loop. SsMTAPII is extremely thermoactive and thermostable. The three-dimensional structure of SsMTAPII suggests that the unique dimer-of-trimers quaternary structure, a CXC motif at the C terminus, and two pairs of intrasubunit disulfide bridges may play an important role in its thermal stability.
Zhang
Yan
Y
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853-1301, USA.
Porcelli
Marina
M
Cacciapuoti
Giovanna
G
Ealick
Steven E
SE
D001665:Binding Sites; D018360:Crystallography, X-Ray; D003839:Deoxyadenosines / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry*; D004795:Enzyme Stability; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics; D011683:Purine-Nucleoside Phosphorylase / Q000737:chemistry* / Q000235:genetics; D013379:Substrate Specificity; D048229:Sulfolobus solfataricus / Q000201:enzymology*; D013696:Temperature; D013872:Thionucleosides / Q000737:chemistry
D003839:Deoxyadenosines; D004220:Disulfides; D007527:Isoenzymes; D021122:Protein Subunits; D013872:Thionucleosides; C008500:5'-methylthioadenosine; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase