5k9g: Difference between revisions
New page: '''Unreleased structure''' The entry 5k9g is ON HOLD Authors: Alvarez, J., Stec, B., Swairjo, M.A. Description: Crystal Structure of GTP Cyclohydrolase-IB with Tris [[Category: Unrelea... |
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==Crystal Structure of GTP Cyclohydrolase-IB with Tris== | |||
<StructureSection load='5k9g' size='340' side='right'caption='[[5k9g]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</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='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> | |||
== Function == | |||
[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;"> | |||
== 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<ref>PMID:28126741</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5k9g" style="background-color:#fffaf0;"></div> | ||
[[Category: Alvarez | |||
[[Category: Swairjo | ==See Also== | ||
*[[Cyclohydrolase 3D structures|Cyclohydrolase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Neisseria gonorrhoeae FA 1090]] | |||
[[Category: Alvarez J]] | |||
[[Category: Stec B]] | |||
[[Category: Swairjo MA]] | |||
Latest revision as of 12:14, 25 October 2023
Crystal Structure of GTP Cyclohydrolase-IB with TrisCrystal Structure of GTP Cyclohydrolase-IB with Tris
Structural highlights
FunctionGCH4_NEIG1 Converts GTP to 7,8-dihydroneopterin triphosphate.[1] Publication Abstract from PubMedGuanosine 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 AlsoReferences
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