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| | <StructureSection load='3a6g' size='340' side='right'caption='[[3a6g]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='3a6g' size='340' side='right'caption='[[3a6g]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3a6g]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_fluorescens_putidus"_flugge_1886 "bacillus fluorescens putidus" flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3A6G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3A6G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3a6g]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_putida Pseudomonas putida]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3A6G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3A6G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1j2t|1j2t]], [[1j2u|1j2u]], [[1v7z|1v7z]], [[3a6d|3a6d]], [[3a6e|3a6e]], [[3a6f|3a6f]], [[3a6h|3a6h]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Creatininase Creatininase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.10 3.5.2.10] </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=3a6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3a6g OCA], [https://pdbe.org/3a6g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3a6g RCSB], [https://www.ebi.ac.uk/pdbsum/3a6g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3a6g 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=3a6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3a6g OCA], [https://pdbe.org/3a6g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3a6g RCSB], [https://www.ebi.ac.uk/pdbsum/3a6g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3a6g ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CRNA_PSEPU CRNA_PSEPU]] Cyclic amidohydrolase that catalyzes the reversible conversion of creatinine to creatine. Is also active toward glycocyamidine, though the reaction rate is very low, but it is completely inert toward hydantoin and its derivatives.<ref>PMID:500580</ref>
| + | [https://www.uniprot.org/uniprot/CRNA_PSEPU CRNA_PSEPU] Cyclic amidohydrolase that catalyzes the reversible conversion of creatinine to creatine. Is also active toward glycocyamidine, though the reaction rate is very low, but it is completely inert toward hydantoin and its derivatives.<ref>PMID:500580</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus fluorescens putidus flugge 1886]] | |
| - | [[Category: Creatininase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ito, K]] | + | [[Category: Pseudomonas putida]] |
| - | [[Category: Nakajima, Y]] | + | [[Category: Ito K]] |
| - | [[Category: Yamashita, K]] | + | [[Category: Nakajima Y]] |
| - | [[Category: Yoshimoto, T]] | + | [[Category: Yamashita K]] |
| - | [[Category: Creatinine amidohydrolase]]
| + | [[Category: Yoshimoto T]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Urease-related amidohydrolase superfamily]]
| + | |
| Structural highlights
Function
CRNA_PSEPU Cyclic amidohydrolase that catalyzes the reversible conversion of creatinine to creatine. Is also active toward glycocyamidine, though the reaction rate is very low, but it is completely inert toward hydantoin and its derivatives.[1]
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
Creatininase is a binuclear zinc enzyme and catalyzes the reversible conversion of creatinine to creatine. It exhibits an open-closed conformational change upon substrate binding, and the differences in the conformations of Tyr121, Trp154, and the loop region containing Trp174 were evident in the enzyme-creatine complex when compared to those in the ligand-free enzyme. We have determined the crystal structure of the enzyme complexed with a 1-methylguanidine. All subunits in the complex existed as the closed form, and the binding mode of creatinine was estimated. Site-directed mutagenesis revealed that the hydrophobic residues that show conformational change upon substrate binding are important for the enzyme activity. We propose a catalytic mechanism of creatininase in which two water molecules have significant roles. The first molecule is a hydroxide ion (Wat1) that is bound as a bridge between the two metal ions and attacks the carbonyl carbon of the substrate. The second molecule is a water molecule (Wat2) that is bound to the carboxyl group of Glu122 and functions as a proton donor in catalysis. The activity of the E122Q mutant was very low and it was only partially restored by the addition of ZnCl(2) or MnCl(2). In the E122Q mutant, k(cat) is drastically decreased, indicating that Glu122 is important for catalysis. X-ray crystallographic study and the atomic absorption spectrometry analysis of the E122Q mutant-substrate complex revealed that the drastic decrease of the activity of the E122Q was caused by not only the loss of one Zn ion at the Metal1 site but also a critical function of Glu122, which most likely exists for a proton transfer step through Wat2.
Substitution of Glu122 by glutamine revealed the function of the second water molecule as a proton donor in the binuclear metal enzyme creatininase.,Yamashita K, Nakajima Y, Matsushita H, Nishiya Y, Yamazawa R, Wu YF, Matsubara F, Oyama H, Ito K, Yoshimoto T J Mol Biol. 2010 Mar 5;396(4):1081-96. Epub 2010 Jan 4. PMID:20043918[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rikitake K, Oka I, Ando M, Yoshimoto T, Tsuru D. Creatinine amidohydrolase (creatininase) from Pseudomonas putida. Purification and some properties. J Biochem. 1979 Oct;86(4):1109-17. PMID:500580
- ↑ Yamashita K, Nakajima Y, Matsushita H, Nishiya Y, Yamazawa R, Wu YF, Matsubara F, Oyama H, Ito K, Yoshimoto T. Substitution of Glu122 by glutamine revealed the function of the second water molecule as a proton donor in the binuclear metal enzyme creatininase. J Mol Biol. 2010 Mar 5;396(4):1081-96. Epub 2010 Jan 4. PMID:20043918 doi:10.1016/j.jmb.2009.12.045
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