3OZB
Crystal Structure of 5'-methylthioinosine phosphorylase from Psedomonas aeruginosa in complex with hypoxanthine
Summary for 3OZB
| Entry DOI | 10.2210/pdb3ozb/pdb |
| Descriptor | Methylthioadenosine phosphorylase, HYPOXANTHINE, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | 5'-methylthioinosine, phosphorylase, transferase |
| Biological source | Pseudomonas aeruginosa |
| Total number of polymer chains | 6 |
| Total formula weight | 169866.80 |
| Authors | Ho, M.,Guan, R.,Almo, S.C.,Schramm, V.L. (deposition date: 2010-09-24, release date: 2011-08-10, Last modification date: 2024-02-21) |
| Primary citation | Guan, R.,Ho, M.C.,Almo, S.C.,Schramm, V.L. Methylthioinosine phosphorylase from Pseudomonas aeruginosa. Structure and annotation of a novel enzyme in quorum sensing. Biochemistry, 50:1247-1254, 2011 Cited by PubMed Abstract: The PA3004 gene of Pseudomonas aeruginosa PAO1 was originally annotated as a 5'-methylthioadenosine phosphorylase (MTAP). However, the PA3004 encoded protein uses 5'-methylthioinosine (MTI) as a preferred substrate and represents the only known example of a specific MTI phosphorylase (MTIP). MTIP does not utilize 5'-methylthioadenosine (MTA). Inosine is a weak substrate with a k(cat)/K(m) value 290-fold less than MTI and is the second best substrate identified. The crystal structure of P. aeruginosa MTIP (PaMTIP) in complex with hypoxanthine was determined to 2.8 Å resolution and revealed a 3-fold symmetric homotrimer. The methylthioribose and phosphate binding regions of PaMTIP are similar to MTAPs, and the purine binding region is similar to that of purine nucleoside phosphorylases (PNPs). The catabolism of MTA in P. aeruginosa involves deamination to MTI and phosphorolysis to hypoxanthine (MTA → MTI → hypoxanthine). This pathway also exists in Plasmodium falciparum, where the purine nucleoside phosphorylase (PfPNP) acts on both inosine and MTI. Three tight-binding transition state analogue inhibitors of PaMTIP are identified with dissociation constants in the picomolar range. Inhibitor specificity suggests an early dissociative transition state for PaMTIP. Quorum sensing molecules are associated with MTA metabolism in bacterial pathogens suggesting PaMTIP as a potential therapeutic target. PubMed: 21197954DOI: 10.1021/bi101642d PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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