Steve Ealick's Research Group


5′-Deoxy-5′-methylthioadenosine Phosphorylase II from Sulfolobus solfataricus


PDB files:

2A8Y, SsMTAPII + MTA + sulfate (P1 space group)

*3T94 corrected to space group C2

Description:

Two different 5′-deoxy-5′-methylthioadenosine phosphorylases (MTAPs) have been isolated from S. solfataricus: SsMTAP and SsMTAPII. SsMTAP can utilize inosine, guanosine, adenosine, and 5′-deoxy-5′-methylthioadenosine (MTA) as substrates and is a homohexamer consisting of six identical subunits of 26.5 kDa. SsMTAPII is a homohexamer with 270 residues and about 30 kDa for each subunit. Unlike hMTAP or SsMTAP, SsMTAPII takes both MTA and adenosine as substrates, with a very high affinity for the former.The structure of SsMTAP II was originally determined in space group P1 (PDB entry 2a8y) and showed R32 pseudosymmetry. Post-analysis using phenix.xtriage showed that the correct space group is C2.

The monomers of SsMTAP are identical subunits of approximately 30 kDa each. The overall fold of each SsMTAPII monomer is a single α/β domain. Sulfate and MTA are shown bound at the active site.

 

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The molecule displays D3 symmetry and can be described as a trimer of dimers with three symmetric intersubunit disulfide bonds linking the dimers to one another. The hexameric shape is similar to that of E. coli purine nucleoside phosphorylase and the previously determined SsMTAP.

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The active site of SsMTAPII is located near the subunit-subunit interface within a trimer but away from the trimer-trimer interface within the hexamer. The binding of the purine base occurs through extensive hydrogen bonding between the enzyme and the ligand. In contrast, the methylthioribose only forms two hydrogen bonds with the enzyme:

 

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References:

Zhang Y, Porcelli M, Cacciapuoti G and Ealick SE.The Crystal Structure of 5′-Deoxy-5′-Methylthioadenosine Phosphorylase II from Sulfolobus solfataricus, A Thermophilic Enzyme Stabilized by Intramolecular Disulfide Bonds. J. Mol. Biol. 357:252-262 (2006).

*Zhang Y, Zwart PH, and Ealick SE. A corrected space group for Sulfolobus sulfataricus 5'-deoxy-5'-methylthioadenosine phosphorylase II. Acta Crystallogr. D 68:249-252 (2012).



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