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1eep
From Proteopedia
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'''2.4 A RESOLUTION CRYSTAL STRUCTURE OF BORRELIA BURGDORFERI INOSINE 5'-MONPHOSPHATE DEHYDROGENASE IN COMPLEX WITH A SULFATE ION''' | '''2.4 A RESOLUTION CRYSTAL STRUCTURE OF BORRELIA BURGDORFERI INOSINE 5'-MONPHOSPHATE DEHYDROGENASE IN COMPLEX WITH A SULFATE ION''' | ||
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[[Category: Ringe, D.]] | [[Category: Ringe, D.]] | ||
[[Category: White, A.]] | [[Category: White, A.]] | ||
| - | [[Category: | + | [[Category: Alpha-beta barrel]] |
| - | [[Category: | + | [[Category: Imp dehydrogenase]] |
| - | [[Category: | + | [[Category: Impdh]] |
| - | [[Category: | + | [[Category: Loop-6]] |
| - | [[Category: | + | [[Category: Purine biosynthesis]] |
| - | [[Category: | + | [[Category: Tim barrel]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 15:00:16 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 12:00, 2 May 2008
2.4 A RESOLUTION CRYSTAL STRUCTURE OF BORRELIA BURGDORFERI INOSINE 5'-MONPHOSPHATE DEHYDROGENASE IN COMPLEX WITH A SULFATE ION
Overview
The conversion of inosine 5'-monophosphate (IMP) to xanthosine 5'-monophosphate (XMP) is the committed and rate-limiting reaction in de novo guanine nucleotide biosynthesis. Inosine 5'- monophosphate dehydrogenase (IMPDH) is the enzyme that catalyzes the oxidation of IMP to XMP with the concomitant reduction of nicotinamide adenine dinucleotide (from NAD(+) to NADH). Because of its critical role in purine biosynthesis, IMPDH is a drug design target for anticancer, antiinfective, and immunosuppressive chemotherapy. We have determined the crystal structure of IMPDH from Borrelia burgdorferi, the bacterial spirochete that causes Lyme disease, with a sulfate ion bound in the IMP phosphate binding site. This is the first structure of IMPDH in the absence of substrate or cofactor where the active-site loop (loop 6), which contains the essential catalytic residue Cys 229, is clearly defined in the electron density. We report that a seven residue region of loop 6, including Cys229, is tilted more than 6 A away from its position in substrate- or substrate analogue-bound structures of IMPDH, suggestive of a conformational change. The location of this loop between beta6 and alpha6 links IMPDH to a family of beta/alpha barrel enzymes known to utilize this loop as a functional lid during catalysis. Least-squares minimization, root-mean-square deviation analysis, and inspection of the molecular surface of the loop 6 region in the substrate-free B. burgdorferi IMPDH and XMP-bound Chinese hamster IMPDH show that loop 6 follows a similar pattern of hinged rigid-body motion and indicates that IMPDH may be using loop 6 to bind and sequester substrate and to recruit an essential catalytic residue.
About this Structure
1EEP is a Single protein structure of sequence from Borrelia burgdorferi. Full crystallographic information is available from OCA.
Reference
Crystal structure at 2.4 A resolution of Borrelia burgdorferi inosine 5'-monophosphate dehydrogenase: evidence of a substrate-induced hinged-lid motion by loop 6., McMillan FM, Cahoon M, White A, Hedstrom L, Petsko GA, Ringe D, Biochemistry. 2000 Apr 18;39(15):4533-42. PMID:10758003 Page seeded by OCA on Fri May 2 15:00:16 2008
