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| | <StructureSection load='5k9g' size='340' side='right'caption='[[5k9g]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='5k9g' size='340' side='right'caption='[[5k9g]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5k9g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Neig1 Neig1]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3d1t 3d1t]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K9G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K9G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5k9g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_gonorrhoeae_FA_1090 Neisseria gonorrhoeae FA 1090]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3d1t 3d1t]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K9G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K9G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=SNC:S-NITROSO-CYSTEINE'>SNC</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SNC:S-NITROSO-CYSTEINE'>SNC</scene></td></tr>
| + | |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[5k95|5k95]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">folE2, NGO0387 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=242231 NEIG1])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/GTP_cyclohydrolase_I GTP cyclohydrolase I], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.16 3.5.4.16] </span></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=5k9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k9g OCA], [https://pdbe.org/5k9g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k9g RCSB], [https://www.ebi.ac.uk/pdbsum/5k9g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k9g ProSAT]</span></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=5k9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k9g OCA], [https://pdbe.org/5k9g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k9g RCSB], [https://www.ebi.ac.uk/pdbsum/5k9g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k9g ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GCH4_NEIG1 GCH4_NEIG1]] Converts GTP to 7,8-dihydroneopterin triphosphate.<ref>PMID:17032654</ref>
| + | [https://www.uniprot.org/uniprot/GCH4_NEIG1 GCH4_NEIG1] Converts GTP to 7,8-dihydroneopterin triphosphate.<ref>PMID:17032654</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: GTP cyclohydrolase I]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Neig1]] | + | [[Category: Neisseria gonorrhoeae FA 1090]] |
| - | [[Category: Alvarez, J]] | + | [[Category: Alvarez J]] |
| - | [[Category: Stec, B]] | + | [[Category: Stec B]] |
| - | [[Category: Swairjo, M A]] | + | [[Category: Swairjo MA]] |
| - | [[Category: Biosynthetic protein]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
GCH4_NEIG1 Converts GTP to 7,8-dihydroneopterin triphosphate.[1]
Publication Abstract from PubMed
Guanosine 5'-triphosphate (GTP) cyclohydrolase-I (GCYH-I) catalyzes the first step in folic acid biosynthesis in bacteria and plants, biopterin biosynthesis in mammals, and the biosynthesis of 7-deazaguanosine-modified tRNA nucleosides in bacteria and archaea. The type IB GCYH (GCYH-IB) is a prokaryotic-specific enzyme found in many pathogens. GCYH-IB is structurally distinct from the canonical type IA GCYH involved in biopterin biosynthesis in humans and animals, and thus is of interest as a potential antibacterial drug target. We report kinetic and inhibition data of Neisseria gonorrhoeae GCYH-IB and two high-resolution crystal structures of the enzyme; one in complex with the reaction intermediate analog and competitive inhibitor 8-oxoguanosine 5'-triphosphate (8-oxo-GTP), and one with a tris(hydroxymethyl)aminomethane molecule bound in the active site and mimicking another reaction intermediate. Comparison with the type IA enzyme bound to 8-oxo-GTP (guanosine 5'-triphosphate) reveals an inverted mode of binding of the inhibitor ribosyl moiety and, together with site-directed mutagenesis data, shows that the two enzymes utilize different strategies for catalysis. Notably, the inhibitor interacts with a conserved active-site Cys149, and this residue is S-nitrosylated in the structures. This is the first structural characterization of a biologically S-nitrosylated bacterial protein. Mutagenesis and biochemical analyses demonstrate that Cys149 is essential for the cyclohydrolase reaction, and S-nitrosylation maintains enzyme activity, suggesting a potential role of the S-nitrosothiol in catalysis.
Mechanism and catalytic strategy of the prokaryotic-specific GTP cyclohydrolase-IB.,Paranagama N, Bonnett SA, Alvarez J, Luthra A, Stec B, Gustafson A, Iwata-Reuyl D, Swairjo MA Biochem J. 2017 Mar 7;474(6):1017-1039. doi: 10.1042/BCJ20161025. PMID:28126741[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ El Yacoubi B, Bonnett S, Anderson JN, Swairjo MA, Iwata-Reuyl D, de Crecy-Lagard V. Discovery of a new prokaryotic type I GTP cyclohydrolase family. J Biol Chem. 2006 Dec 8;281(49):37586-93. Epub 2006 Oct 10. PMID:17032654 doi:10.1074/jbc.M607114200
- ↑ Paranagama N, Bonnett SA, Alvarez J, Luthra A, Stec B, Gustafson A, Iwata-Reuyl D, Swairjo MA. Mechanism and catalytic strategy of the prokaryotic-specific GTP cyclohydrolase-IB. Biochem J. 2017 Mar 7;474(6):1017-1039. doi: 10.1042/BCJ20161025. PMID:28126741 doi:http://dx.doi.org/10.1042/BCJ20161025
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