1eep

<table><tr><td colspan='2'>[[1eep]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_35210 Atcc 35210]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EEP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EEP FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1eep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1eep OCA], [http://pdbe.org/1eep PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1eep RCSB], [http://www.ebi.ac.uk/pdbsum/1eep PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1eep ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/IMDH_BORBU IMDH_BORBU]] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Essential for mouse infection by tick bite and critical for the survival in environments that appear to lack sufficient amounts of guanine, guanosine, and/or deoxyguanosine to support spirochete growth, such as mammalian host tissues.<ref>PMID:9268334</ref> <ref>PMID:19666713</ref>

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

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.

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<ref>PMID:10758003</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

</div>

<div class="pdbe-citations 1eep" style="background-color:#fffaf0;"></div>

[[Category: Atcc 35210]]

[[Category: IMP dehydrogenase]]

[[Category: Cahoon, M]]

[[Category: Hedstrom, L]]

[[Category: McMillan, F M]]

[[Category: Petsko, G A]]

[[Category: Ringe, D]]

[[Category: White, A]]

[[Category: Tim barrel]]