1meh

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{{STRUCTURE_1meh| PDB=1meh | SCENE= }}
{{STRUCTURE_1meh| PDB=1meh | SCENE= }}
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'''Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with IMP and MOA bound'''
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===Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with IMP and MOA bound===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 12559919 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12559919}}
==About this Structure==
==About this Structure==
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[[Category: Prosise, G L.]]
[[Category: Prosise, G L.]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:56:31 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 23:47:26 2008''

Revision as of 20:47, 2 July 2008

Image:1meh.png

Template:STRUCTURE 1meh

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

Template:ABSTRACT PUBMED 12559919

About this Structure

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

Reference

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

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