1a8r: Difference between revisions

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New page: left|200px<br /><applet load="1a8r" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a8r, resolution 2.1Å" /> '''GTP CYCLOHYDROLASE I ...
 
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[[Image:1a8r.gif|left|200px]]<br /><applet load="1a8r" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1a8r, resolution 2.1&Aring;" />
'''GTP CYCLOHYDROLASE I (H112S MUTANT) IN COMPLEX WITH GTP'''<br />


==Overview==
==GTP CYCLOHYDROLASE I (H112S MUTANT) IN COMPLEX WITH GTP==
GTP cyclohydrolase I catalyses the hydrolytic release of formate from GTP, followed by cyclization to dihydroneopterin triphosphate. The enzymes from, bacteria and animals are homodecamers containing one zinc ion per subunit., Replacement of Cys110, Cys181, His112 or His113 of the enzyme from, Escherichia coli by serine affords catalytically inactive mutant proteins, with reduced capacity to bind zinc. These mutant proteins are unable to, convert GTP or the committed reaction intermediate, 2-amino-5-formylamino-6-(beta-ribosylamino)-4(3H)-pyrimidinone, 5'-triphosphate, to dihydroneopterin triphosphate. The crystal structures, of GTP complexes of the His113Ser, His112Ser and Cys181Ser mutant proteins, determined at resolutions of 2.5A, 2.8A and 3.2A, respectively, revealed, the conformation of substrate GTP in the active site cavity. The, carboxylic group of the highly conserved residue Glu152 anchors the, substrate GTP, by hydrogen bonding to N-3 and to the position 2 amino, group. Several basic amino acid residues interact with the triphosphate, moiety of the substrate. The structure of the His112Ser mutant in complex, with an undefined mixture of nucleotides determined at a resolution of, 2.1A afforded additional details of the peptide folding. Comparison, between the wild-type and mutant enzyme structures indicates that the, catalytically active zinc ion is directly coordinated to Cys110, Cys181, and His113. Moreover, the zinc ion is complexed to a water molecule, which, is in close hydrogen bond contact to His112. In close analogy to zinc, proteases, the zinc-coordinated water molecule is suggested to attack C-8, of the substrate affording a zinc-bound 8R hydrate of GTP. Opening of the, hydrated imidazole ring affords a formamide derivative, which remains, coordinated to zinc. The subsequent hydrolysis of the formamide motif has, an absolute requirement for zinc ion catalysis. The hydrolysis of the, formamide bond shows close mechanistic similarity with peptide hydrolysis, by zinc proteases.
<StructureSection load='1a8r' size='340' side='right'caption='[[1a8r]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1a8r]] is a 15 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A8R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A8R FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1a8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a8r OCA], [https://pdbe.org/1a8r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a8r RCSB], [https://www.ebi.ac.uk/pdbsum/1a8r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a8r ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GCH1_ECOLI GCH1_ECOLI]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a8/1a8r_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/main_output.php?pdb_ID=1a8r ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1A8R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with GTP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/GTP_cyclohydrolase_I GTP cyclohydrolase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.16 3.5.4.16] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1A8R OCA].
*[[Cyclohydrolase 3D structures|Cyclohydrolase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Biosynthesis of pteridines. Reaction mechanism of GTP cyclohydrolase I., Rebelo J, Auerbach G, Bader G, Bracher A, Nar H, Hosl C, Schramek N, Kaiser J, Bacher A, Huber R, Fischer M, J Mol Biol. 2003 Feb 14;326(2):503-16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12559918 12559918]
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: GTP cyclohydrolase I]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Auerbach G]]
[[Category: Auerbach, G.]]
[[Category: Bacher A]]
[[Category: Bacher, A.]]
[[Category: Bracher A]]
[[Category: Bracher, A.]]
[[Category: Huber R]]
[[Category: Huber, R.]]
[[Category: Nar H]]
[[Category: Nar, H.]]
[[Category: GTP]]
[[Category: gtp]]
[[Category: hydrolase]]
[[Category: pterine synthesis]]
[[Category: purine hydrolysis]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 10:41:04 2007''

Latest revision as of 09:28, 7 February 2024

GTP CYCLOHYDROLASE I (H112S MUTANT) IN COMPLEX WITH GTPGTP CYCLOHYDROLASE I (H112S MUTANT) IN COMPLEX WITH GTP

Structural highlights

1a8r is a 15 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.1Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GCH1_ECOLI

Evolutionary Conservation

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

See Also

1a8r, resolution 2.10Å

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