Steve Ealick's Research Group

Human 5'-Deoxy-5′-Methylthioadenosine Phosphorylase

PDB files:

1CB0 (MTAP with adenine)

1CG6 (MTAP with MTA and sulfate)

*1SD1(MTAP with Formycin A)

*1SD2 (MTAP with 5′-methylthiotubercidin (MTT))


5′-Deoxy-5′-methylthioadenosine phosphorylase (MTAP) catalyzes the reversible phosphorolysis of 5′-deoxy-5′- methylthioadenosine (MTA) to adenine and 5-methylthio-D-ribose-1- phosphate. We have determined the crystal structure of MTAP at 1.7 Å resolution using multiwavelength anomalous diffraction phasing techniques.

Each subunit consists of a single αβ domain containing a central eight-stranded mixed β-sheet, a smaller five-stranded mixed β-sheet and six α-helices. The β-sheets are the flat green arrows, while the α-helices are blue. The refined positions of the MTA and sulfate are shown with ball-and-stick models.

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MTAP is a trimer comprised of three identical subunits. Ball-and-stick models of MTA and sulfate are shown in each of the three active sites.

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The active site of MTAP contains three distinct regions corresponding to the base-, methylthioribose-, and sulfate/phosphate binding sites. Click here to see the orientation of ligands with respect to important active site residues.


Appleby TC, Erion MD, and Ealick SE. The structure of Human 5′-Deoxy-5′-Methylthioadenosine Phosphorylase at 1.7 Å Resolution Provides Insights into Substrate Binding and Catalysis. Structure 7:629-641 (1999).

*Lee JE, Settembre EC, Cornell KA, Riscoe MK, Sufrin JR, Ealick SE, and Howell PL. Structural comparison of MTA phosphorylase and MTA/AdoHcy nucleosidase explains substrate preferences and identifies regions exploitable for inhibitor design. Biochemistry 43: 5159-5169 (2004).

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