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| | ==Crystal structure of dipeptidase from Streptomics coelicolor complexed with phosphinate pseudodipeptide L-Ala-D-Asp at 1.4A resolution.== | | ==Crystal structure of dipeptidase from Streptomics coelicolor complexed with phosphinate pseudodipeptide L-Ala-D-Asp at 1.4A resolution.== |
| - | <StructureSection load='3k5x' size='340' side='right' caption='[[3k5x]], [[Resolution|resolution]] 1.40Å' scene=''> | + | <StructureSection load='3k5x' size='340' side='right'caption='[[3k5x]], [[Resolution|resolution]] 1.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3k5x]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"actinomyces_coelicolor"_(muller_1908)_lieske_1921 "actinomyces coelicolor" (muller 1908) lieske 1921]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3K5X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3K5X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3k5x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_coelicolor Streptomyces coelicolor]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3K5X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3K5X FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P8D:PHOSPHINATE+PSEUDODIPEPTIDE+L-ALA-D-ASP'>P8D</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]] 1.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3id7|3id7]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P8D:PHOSPHINATE+PSEUDODIPEPTIDE+L-ALA-D-ASP'>P8D</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SCO3058, SCBAC19G2.13c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1902 "Actinomyces coelicolor" (Muller 1908) Lieske 1921])</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=3k5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k5x OCA], [https://pdbe.org/3k5x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3k5x RCSB], [https://www.ebi.ac.uk/pdbsum/3k5x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3k5x ProSAT]</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=3k5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k5x OCA], [http://pdbe.org/3k5x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3k5x RCSB], [http://www.ebi.ac.uk/pdbsum/3k5x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3k5x ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q93J45_STRCO Q93J45_STRCO] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k5/3k5x_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k5/3k5x_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Almo, S C]] | + | [[Category: Large Structures]] |
| - | [[Category: Cummings, J]] | + | [[Category: Streptomyces coelicolor]] |
| - | [[Category: Fedorov, A A]] | + | [[Category: Almo SC]] |
| - | [[Category: Fedorov, E V]] | + | [[Category: Cummings J]] |
| - | [[Category: Raushel, F M]] | + | [[Category: Fedorov AA]] |
| - | [[Category: Dipeptidase from streptomics coelicolor]] | + | [[Category: Fedorov EV]] |
| - | [[Category: Hydrolase]] | + | [[Category: Raushel FM]] |
| - | [[Category: L-ala-d-asp]]
| + | |
| - | [[Category: Phosphinate pseudodipeptide]]
| + | |
| - | [[Category: The closest bacterial homolog to human renal dipeptidase]]
| + | |
| Structural highlights
Function
Q93J45_STRCO
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
Human renal dipeptidase, an enzyme associated with glutathione metabolism and the hydrolysis of beta-lactams, is similar in sequence to a cluster of approximately 400 microbial proteins currently annotated as nonspecific dipeptidases within the amidohydrolase superfamily. The closest homologue to the human renal dipeptidase from a fully sequenced microbe is Sco3058 from Streptomyces coelicolor. Dipeptide substrates of Sco3058 were identified by screening a comprehensive series of l-Xaa-l-Xaa, l-Xaa-d-Xaa, and d-Xaa-l-Xaa dipeptide libraries. The substrate specificity profile shows that Sco3058 hydrolyzes a broad range of dipeptides with a marked preference for an l-amino acid at the N-terminus and a d-amino acid at the C-terminus. The best substrate identified was l-Arg-d-Asp (k(cat)/K(m) = 7.6 x 10(5) M(-1) s(-1)). The three-dimensional structure of Sco3058 was determined in the absence and presence of the inhibitors citrate and a phosphinate mimic of l-Ala-d-Asp. The enzyme folds as a (beta/alpha)(8) barrel, and two zinc ions are bound in the active site. Site-directed mutagenesis was used to probe the importance of specific residues that have direct interactions with the substrate analogues in the active site (Asp-22, His-150, Arg-223, and Asp-320). The solvent viscosity and kinetic effects of D(2)O indicate that substrate binding is relatively sticky and that proton transfers do not occurr during the rate-limiting step. A bell-shaped pH-rate profile for k(cat) and k(cat)/K(m) indicated that one group needs to be deprotonated and a second group must be protonated for optimal turnover. Computational docking of high-energy intermediate forms of l/d-Ala-l/d-Ala to the three-dimensional structure of Sco3058 identified the structural determinants for the stereochemical preferences for substrate binding and turnover.
Structure, Mechanism, and Substrate Profile for Sco3058: The Closest Bacterial Homologue to Human Renal Dipeptidase .,Cummings JA, Nguyen TT, Fedorov AA, Kolb P, Xu C, Fedorov EV, Shoichet BK, Barondeau DP, Almo SC, Raushel FM Biochemistry. 2009 Dec 29. PMID:20000809[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cummings JA, Nguyen TT, Fedorov AA, Kolb P, Xu C, Fedorov EV, Shoichet BK, Barondeau DP, Almo SC, Raushel FM. Structure, Mechanism, and Substrate Profile for Sco3058: The Closest Bacterial Homologue to Human Renal Dipeptidase . Biochemistry. 2009 Dec 29. PMID:20000809 doi:10.1021/bi901935y
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