From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1me8.jpg|left|200px]] | + | {{Seed}} |
| | + | [[Image:1me8.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1me8| PDB=1me8 | SCENE= }} | | {{STRUCTURE_1me8| PDB=1me8 | SCENE= }} |
| | | | |
| - | '''Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with RVP bound'''
| + | ===Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with RVP bound=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | Inosine monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step in GMP biosynthesis. The resulting intracellular pool of guanine nucleotides is of great importance to all cells for use in DNA and RNA synthesis, metabolism, and signal transduction. The enzyme binds IMP and the cofactor NAD(+) in random order, IMP is converted to XMP, NAD(+) is reduced to NADH, and finally, NADH and then XMP are released sequentially. XMP is subsequently converted into GMP by GMP synthetase. Drugs that decrease GMP synthesis by inhibiting IMPDH have been shown to have antiproliferative as well as antiviral activity. Several drugs are in use that target the substrate- or cofactor-binding site; however, due to differences between the mammalian and microbial isoforms, most drugs are far less effective against the microbial form of the enzyme than the mammalian form. The high resolution crystal structures of the protozoan parasite Tritrichomonas foetus IMPDH complexed with the inhibitor ribavirin monophosphate as well as monophosphate together with a second inhibitor, mycophenolic acid, are presented here. These structures reveal an active site cation identified previously only in the Chinese hamster IMPDH structure with covalently bound IMP. This cation was not found previously in apo IMPDH, IMPDH in complex with XMP, or covalently bound inhibitor, indicating that the cation-binding site may be catalysis-dependent. A comparison of T. foetus IMPDH with the Chinese hamster and Streptococcus pyogenes structures reveals differences in the active site loop architecture, which contributes to differences in cation binding during the catalytic sequence and the kinetic rates between bacterial, protozoan, and mammalian enzymes. Exploitation of these differences may lead to novel inhibitors, which favor the microbial form of the enzyme.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_12235158}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 12235158 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_12235158}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 27: |
Line 31: |
| | [[Category: Wu, J.]] | | [[Category: Wu, J.]] |
| | [[Category: Alpha beta barrel]] | | [[Category: Alpha beta barrel]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:56:12 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 23:46:54 2008'' |
Revision as of 20:46, 2 July 2008
Template:STRUCTURE 1me8
Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with RVP bound
Template:ABSTRACT PUBMED 12235158
About this Structure
1ME8 is a Single protein structure of sequence from Tritrichomonas foetus. Full crystallographic information is available from OCA.
Reference
Crystal structure of Tritrichomonas foetus inosine monophosphate dehydrogenase in complex with the inhibitor ribavirin monophosphate reveals a catalysis-dependent ion-binding site., Prosise GL, Wu JZ, Luecke H, J Biol Chem. 2002 Dec 27;277(52):50654-9. Epub 2002 Sep 13. PMID:12235158
Page seeded by OCA on Wed Jul 2 23:46:54 2008
