1cb0
From Proteopedia
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'''STRUCTURE OF HUMAN 5'-DEOXY-5'-METHYLTHIOADENOSINE PHOSPHORYLASE AT 1.7 A RESOLUTION''' | '''STRUCTURE OF HUMAN 5'-DEOXY-5'-METHYLTHIOADENOSINE PHOSPHORYLASE AT 1.7 A RESOLUTION''' | ||
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[[Category: Ealick, S E.]] | [[Category: Ealick, S E.]] | ||
[[Category: Erion, M D.]] | [[Category: Erion, M D.]] | ||
| - | [[Category: | + | [[Category: Adenine]] |
| - | [[Category: | + | [[Category: Methylthioadenosine phosphorylase]] |
| - | [[Category: | + | [[Category: Purine nucleoside phosphorylase]] |
| - | [[Category: | + | [[Category: Purine salvage]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 12:32:18 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 09:32, 2 May 2008
STRUCTURE OF HUMAN 5'-DEOXY-5'-METHYLTHIOADENOSINE PHOSPHORYLASE AT 1.7 A RESOLUTION
Overview
BACKGROUND: 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. MTA is a by-product of polyamine biosynthesis, which is essential for cell growth and proliferation. This salvage reaction is the principle source of free adenine in human cells. Because of its importance in coupling the purine salvage pathway to polyamine biosynthesis MTAP is a potential chemotherapeutic target. RESULTS: We have determined the crystal structure of MTAP at 1.7 A resolution using multiwavelength anomalous diffraction phasing techniques. MTAP is a trimer comprised of three identical subunits. Each subunit consists of a single alpha/beta domain containing a central eight-stranded mixed beta sheet, a smaller five-stranded mixed beta sheet and six alpha helices. The native structure revealed the presence of an adenine molecule in the purine-binding site. The structure of MTAP with methylthioadenosine and sulfate ion soaked into the active site was also determined using diffraction data to 1.7 A resolution. CONCLUSIONS: The overall quaternary structure and subunit topology of MTAP are similar to mammalian purine nucleoside phosphorylase (PNP). The structures of the MTAP-ligand complexes provide a map of the active site and suggest possible roles for specific residues in substrate binding and catalysis. Residues accounting for the differences in substrate specificity between MTAP and PNP are also identified. Detailed information about the structure and chemical nature of the MTAP active site will aid in the rational design of inhibitors of this potential chemotherapeutic target. The MTAP structure represents the first structure of a mammalian PNP that is specific for 6-aminopurines.
About this Structure
1CB0 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The structure of human 5'-deoxy-5'-methylthioadenosine phosphorylase at 1.7 A resolution provides insights into substrate binding and catalysis., Appleby TC, Erion MD, Ealick SE, Structure. 1999 Jun 15;7(6):629-41. PMID:10404592 Page seeded by OCA on Fri May 2 12:32:18 2008
