1me9: Difference between revisions

Revision as of 00:56, 3 May 2008

Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with IMP bound

OverviewOverview

The enzyme inosine monophosphate dehydrogenase (IMPDH) is responsible for the rate-limiting step in guanine nucleotide biosynthesis. Because it is up-regulated in rapidly proliferating cells, human type II IMPDH is actively targeted for immunosuppressive, anticancer, and antiviral chemotherapy. The enzyme employs a random-in ordered-out kinetic mechanism where substrate or cofactor can bind first but product is only released after the cofactor leaves. Due to structural and kinetic differences between mammalian and microbial enzymes, most drugs that are successful in the inhibition of mammalian IMPDH are far less effective against the microbial forms of the enzyme. It is possible that with greater knowledge of the structural mechanism of the microbial enzymes, an effective and selective inhibitor of microbial IMPDH will be developed for use as a drug against multi-drug resistant bacteria and protists. The high-resolution crystal structures of four different complexes of IMPDH from the protozoan parasite Tritrichomonas foetus have been solved: with its substrate IMP, IMP and the inhibitor mycophenolic acid (MPA), the product XMP with MPA, and XMP with the cofactor NAD(+). In addition, a potassium ion has been located at the dimer interface. A structural model for the kinetic mechanism is proposed.

About this StructureAbout this Structure

1ME9 is a Single protein structure of sequence from Tritrichomonas foetus. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structures of Tritrichomonasfoetus inosine monophosphate dehydrogenase in complex with substrate, cofactor and analogs: a structural basis for the random-in ordered-out kinetic mechanism., Prosise GL, Luecke H, J Mol Biol. 2003 Feb 14;326(2):517-27. PMID:12559919 Page seeded by OCA on Sat May 3 00:56:13 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1me9.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1me9 |SIZE=350|CAPTION= <scene name='initialview01'>1me9</scene>, resolution 2.2&Aring;
+The line below this paragraph, containing "STRUCTURE_1me9", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/IMP_dehydrogenase IMP dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.205 1.1.1.205] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= IMPDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5724 Tritrichomonas foetus])
+-->
-|DOMAIN=
+{{STRUCTURE_1me9|  PDB=1me9  |  SCENE=  }}
-|RELATEDENTRY=[[1ak5|1AK5]], [[1me7|1ME7]], [[1me8|1ME8]], [[1meh|1MEH]], [[1mei|1MEI]], [[1mew|1MEW]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1me9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1me9 OCA], [http://www.ebi.ac.uk/pdbsum/1me9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1me9 RCSB]</span>
-}}
 '''Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with IMP bound'''
@@ Line 28: / Line 25: @@
 [[Category: Luecke, H.]]
 [[Category: Prosise, G L.]]
-[[Category: alpha beta barrel]]
+[[Category: Alpha beta barrel]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 00:56:13 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:14:59 2008''