5k9g: Difference between revisions
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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. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K9G FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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> | |||
<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">[[5k95|5k95]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </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=5k9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k9g OCA], [http://pdbe.org/5k9g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k9g RCSB], [http://www.ebi.ac.uk/pdbsum/5k9g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k9g ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://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 == | |||
GTP cyclohydrolase I (GCYH-I) is an essential Zn(2+)-dependent enzyme that catalyzes the first step of the de novo folate biosynthetic pathway in bacteria and plants, the 7-deazapurine biosynthetic pathway in Bacteria and Archaea, and the biopterin pathway in mammals. We recently reported the discovery of a new prokaryotic-specific GCYH-I (GCYH-IB) that displays no sequence identity to the canonical enzyme and is present in approximately 25% of bacteria, the majority of which lack the canonical GCYH-I (renamed GCYH-IA). Genomic and genetic analyses indicate that in those organisms possessing both enzymes, e.g., Bacillus subtilis, GCYH-IA and -IB are functionally redundant, but differentially expressed. Whereas GCYH-IA is constitutively expressed, GCYH-IB is expressed only under Zn(2+)-limiting conditions. These observations are consistent with the hypothesis that GCYH-IB functions to allow folate biosynthesis during Zn(2+) starvation. Here, we present biochemical and structural data showing that bacterial GCYH-IB, like GCYH-IA, belongs to the tunneling-fold (T-fold) superfamily. However, the GCYH-IA and -IB enzymes exhibit significant differences in global structure and active-site architecture. While GCYH-IA is a unimodular, homodecameric, Zn(2+)-dependent enzyme, GCYH-IB is a bimodular, homotetrameric enzyme activated by a variety of divalent cations. The structure of GCYH-IB and the broad metal dependence exhibited by this enzyme further underscore the mechanistic plasticity that is emerging for the T-fold superfamily. Notably, while humans possess the canonical GCYH-IA enzyme, many clinically important human pathogens possess only the GCYH-IB enzyme, suggesting that this enzyme is a potential new molecular target for antibacterial development. | |||
Zinc-independent folate biosynthesis: genetic, biochemical, and structural investigations reveal new metal dependence for GTP cyclohydrolase IB.,Sankaran B, Bonnett SA, Shah K, Gabriel S, Reddy R, Schimmel P, Rodionov DA, de Crecy-Lagard V, Helmann JD, Iwata-Reuyl D, Swairjo MA J Bacteriol. 2009 Nov;191(22):6936-49. Epub 2009 Sep 18. PMID:19767425<ref>PMID:19767425</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5k9g" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: GTP cyclohydrolase I]] | |||
[[Category: Alvarez, J]] | |||
[[Category: Stec, B]] | [[Category: Stec, B]] | ||
[[Category: | [[Category: Swairjo, M A]] | ||
[[Category: | [[Category: Biosynthetic protein]] | ||
[[Category: Hydrolase]] | |||
Revision as of 19:52, 9 September 2016
Crystal Structure of GTP Cyclohydrolase-IB with TrisCrystal Structure of GTP Cyclohydrolase-IB with Tris
Structural highlights
Function[GCH4_NEIG1] Converts GTP to 7,8-dihydroneopterin triphosphate.[1] Publication Abstract from PubMedGTP cyclohydrolase I (GCYH-I) is an essential Zn(2+)-dependent enzyme that catalyzes the first step of the de novo folate biosynthetic pathway in bacteria and plants, the 7-deazapurine biosynthetic pathway in Bacteria and Archaea, and the biopterin pathway in mammals. We recently reported the discovery of a new prokaryotic-specific GCYH-I (GCYH-IB) that displays no sequence identity to the canonical enzyme and is present in approximately 25% of bacteria, the majority of which lack the canonical GCYH-I (renamed GCYH-IA). Genomic and genetic analyses indicate that in those organisms possessing both enzymes, e.g., Bacillus subtilis, GCYH-IA and -IB are functionally redundant, but differentially expressed. Whereas GCYH-IA is constitutively expressed, GCYH-IB is expressed only under Zn(2+)-limiting conditions. These observations are consistent with the hypothesis that GCYH-IB functions to allow folate biosynthesis during Zn(2+) starvation. Here, we present biochemical and structural data showing that bacterial GCYH-IB, like GCYH-IA, belongs to the tunneling-fold (T-fold) superfamily. However, the GCYH-IA and -IB enzymes exhibit significant differences in global structure and active-site architecture. While GCYH-IA is a unimodular, homodecameric, Zn(2+)-dependent enzyme, GCYH-IB is a bimodular, homotetrameric enzyme activated by a variety of divalent cations. The structure of GCYH-IB and the broad metal dependence exhibited by this enzyme further underscore the mechanistic plasticity that is emerging for the T-fold superfamily. Notably, while humans possess the canonical GCYH-IA enzyme, many clinically important human pathogens possess only the GCYH-IB enzyme, suggesting that this enzyme is a potential new molecular target for antibacterial development. Zinc-independent folate biosynthesis: genetic, biochemical, and structural investigations reveal new metal dependence for GTP cyclohydrolase IB.,Sankaran B, Bonnett SA, Shah K, Gabriel S, Reddy R, Schimmel P, Rodionov DA, de Crecy-Lagard V, Helmann JD, Iwata-Reuyl D, Swairjo MA J Bacteriol. 2009 Nov;191(22):6936-49. Epub 2009 Sep 18. PMID:19767425[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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