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1zfj

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Revision as of 09:19, 2 May 2018

INOSINE MONOPHOSPHATE DEHYDROGENASE (IMPDH; EC 1.1.1.205) FROM STREPTOCOCCUS PYOGENES

Structural highlights

1zfj is a 1 chain structure with sequence from "micrococcus_scarlatinae"_klein_1884 "micrococcus scarlatinae" klein 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Activity:	IMP dehydrogenase, with EC number 1.1.1.205
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IMDH_STRPY] 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 (By similarity).[HAMAP-Rule:MF_01964]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

IMP dehydrogenase (IMPDH) is an essential enzyme that catalyzes the first step unique to GTP synthesis. To provide a basis for the evaluation of IMPDH inhibitors as antimicrobial agents, we have expressed and characterized IMPDH from the pathogenic bacterium Streptococcus pyogenes. Our results show that the biochemical and kinetic characteristics of S. pyogenes IMPDH are similar to other bacterial IMPDH enzymes. However, the lack of sensitivity to mycophenolic acid and the Km for NAD (1180 microM) exemplify some of the differences between the bacterial and mammalian IMPDH enzymes, making it an attractive target for antimicrobial agents. To evaluate the basis for these differences, we determined the crystal structure of the bacterial enzyme at 1.9 A with substrate bound in the catalytic site. The structure was determined using selenomethionine-substituted protein and multiwavelength anomalous (MAD) analysis of data obtained with synchrotron radiation from the undulator beamline (19ID) of the Structural Biology Center at Argonne's Advanced Photon Source. S. pyogenes IMPDH is a tetramer with its four subunits related by a crystallographic 4-fold axis. The protein is composed of two domains: a TIM barrel domain that embodies the catalytic framework and a cystathione beta-synthase (CBS) dimer domain of so far unknown function. Using information provided by sequence alignments and the crystal structure, we prepared several site-specific mutants to examine the role of various active site regions in catalysis. These variants implicate the active site flap as an essential catalytic element and indicate there are significant differences in the catalytic environment of bacterial and mammalian IMPDH enzymes. Comparison of the structure of bacterial IMPDH with the known partial structures from eukaryotic organisms will provide an explanation of their distinct properties and contribute to the design of specific bacterial IMPDH inhibitors.

Characteristics and crystal structure of bacterial inosine-5'-monophosphate dehydrogenase.,Zhang R, Evans G, Rotella FJ, Westbrook EM, Beno D, Huberman E, Joachimiak A, Collart FR Biochemistry. 1999 Apr 13;38(15):4691-700. PMID:10200156^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zhang R, Evans G, Rotella FJ, Westbrook EM, Beno D, Huberman E, Joachimiak A, Collart FR. Characteristics and crystal structure of bacterial inosine-5'-monophosphate dehydrogenase. Biochemistry. 1999 Apr 13;38(15):4691-700. PMID:10200156 doi:10.1021/bi982858v

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1zfj"

@@ Line 1: / Line 1: @@
 ==INOSINE MONOPHOSPHATE DEHYDROGENASE (IMPDH; EC 1.1.1.205) FROM STREPTOCOCCUS PYOGENES==
 <StructureSection load='1zfj' size='340' side='right' caption='[[1zfj]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=1zfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zfj OCA], [http://pdbe.org/1zfj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zfj RCSB], [http://www.ebi.ac.uk/pdbsum/1zfj PDBsum]</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=1zfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zfj OCA], [http://pdbe.org/1zfj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zfj RCSB], [http://www.ebi.ac.uk/pdbsum/1zfj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zfj ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zf/1zfj_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zf/1zfj_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1zfj ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 29: / Line 30: @@
 </div>
 <div class="pdbe-citations 1zfj" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Inosine monophosphate dehydrogenase|Inosine monophosphate dehydrogenase]]
 == References ==
 <references/>

1zfj

From Proteopedia

Revision as of 09:19, 2 May 2018

INOSINE MONOPHOSPHATE DEHYDROGENASE (IMPDH; EC 1.1.1.205) FROM STREPTOCOCCUS PYOGENES

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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