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| | ==Crystal structure of PLP bound Diaminopropionate ammonia lyase from Salmonella typhimurium== | | ==Crystal structure of PLP bound Diaminopropionate ammonia lyase from Salmonella typhimurium== |
| - | <StructureSection load='5ygr' size='340' side='right' caption='[[5ygr]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='5ygr' size='340' side='right'caption='[[5ygr]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ygr]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YGR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YGR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ygr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Salmonella_enterica_subsp._enterica_serovar_Typhi Salmonella enterica subsp. enterica serovar Typhi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YGR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YGR 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=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.5Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene></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=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Diaminopropionate_ammonia-lyase Diaminopropionate ammonia-lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.1.15 4.3.1.15] </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=5ygr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ygr OCA], [https://pdbe.org/5ygr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ygr RCSB], [https://www.ebi.ac.uk/pdbsum/5ygr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ygr 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=5ygr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ygr OCA], [http://pdbe.org/5ygr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ygr RCSB], [http://www.ebi.ac.uk/pdbsum/5ygr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ygr ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/DPAL_SALTY DPAL_SALTY] Catalyzes the alpha,beta-elimination reaction of both L- and D-alpha,beta-diaminopropionate (DAP) to form pyruvate and ammonia. In vitro L- and D-isomers of serine are also degraded, though slowly; it is the only serine dehydratase which can eliminate an amino group at the beta-carbon position. In vivo L-, D- and a mixure of DL-DAP allow growth. DL-DAP is toxic in the absence of this enzyme, it may inhibit enzymes involved in the synthesis of pyruvate and aspartate, as well as amino acids derived from them.<ref>PMID:12821154</ref> <ref>PMID:22904288</ref> <ref>PMID:3275662</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: Diaminopropionate ammonia-lyase]] | + | [[Category: Large Structures]] |
| - | [[Category: Geeta, D]] | + | [[Category: Salmonella enterica subsp. enterica serovar Typhi]] |
| - | [[Category: Murthy, M R.N]]
| + | [[Category: Geeta D]] |
| - | [[Category: Shavithri, H S]] | + | [[Category: Murthy MRN]] |
| - | [[Category: Shveta, B]] | + | [[Category: Shavithri HS]] |
| - | [[Category: Dimer]] | + | [[Category: Shveta B]] |
| - | [[Category: Internal aldimine]] | + | |
| - | [[Category: Lyase]]
| + | |
| Structural highlights
Function
DPAL_SALTY Catalyzes the alpha,beta-elimination reaction of both L- and D-alpha,beta-diaminopropionate (DAP) to form pyruvate and ammonia. In vitro L- and D-isomers of serine are also degraded, though slowly; it is the only serine dehydratase which can eliminate an amino group at the beta-carbon position. In vivo L-, D- and a mixure of DL-DAP allow growth. DL-DAP is toxic in the absence of this enzyme, it may inhibit enzymes involved in the synthesis of pyruvate and aspartate, as well as amino acids derived from them.[1] [2] [3]
Publication Abstract from PubMed
Cellular metabolism of amino acids is controlled by a large number of pyridoxal 5'-phosphate (PLP) dependent enzymes. Diaminopropionate ammonia lyase (DAPAL), a fold type II PLP-dependent enzyme, degrades both the D and L forms of diaminopropionic acid (DAP) to pyruvate and ammonia. Earlier studies on the Escherichia coli DAPAL (EcDAPAL) had suggested that a disulfide bond located close to the active site may be crucial for maintaining the geometry of the substrate entry channel and the active site. In order to obtain further insights into the catalytic properties of DAPAL, structural and functional studies on Salmonella typhimurium DAPAL (StDAPAL) were initiated. The three-dimensional X-ray crystal structure of StDAPAL was determined at 2.5A resolution. As expected, the polypeptide fold and dimeric organization of StDAPAL is similar to those of EcDAPAL. A phosphate group was located in the active site of StDAPAL and expulsion of this phosphate is probably essential to bring Asp125 to a conformation suitable for proton abstraction from the substrate (D-DAP). The unique disulfide bond of EcDAPAL was absent in StDAPAL, although the enzyme displayed comparable catalytic activity. Site directed mutagenesis of the cysteine residues involved in disulfide bond formation in EcDAPAL followed by functional and biophysical studies further confirmed that the disulfide bond is not necessary either for substrate binding or for catalysis. The activity of StDAPAL but not EcDAPAL was enhanced by monovalent cations suggesting subtle differences in the active site geometries of these two closely related enzymes.
Comparative structural and enzymatic studies on Salmonella typhimurium diaminopropionate ammonia lyase reveal its unique features.,Deka G, Bisht S, Savithri HS, Murthy MRN J Struct Biol. 2017 Dec 30. pii: S1047-8477(17)30235-6. doi:, 10.1016/j.jsb.2017.12.012. PMID:29294403[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Khan F, Jala VR, Rao NA, Savithri HS. Characterization of recombinant diaminopropionate ammonia-lyase from Escherichia coli and Salmonella typhimurium. Biochem Biophys Res Commun. 2003 Jul 11;306(4):1083-8. PMID:12821154
- ↑ Kalyani JN, Ramachandra N, Kachroo AH, Mahadevan S, Savithri HS. Functional analysis of the genes encoding diaminopropionate ammonia lyase in Escherichia coli and Salmonella enterica serovar Typhimurium. J Bacteriol. 2012 Oct;194(20):5604-12. Epub 2012 Aug 17. PMID:22904288 doi:http://dx.doi.org/10.1128/JB.01362-12
- ↑ Nagasawa T, Tanizawa K, Satoda T, Yamada H. Diaminopropionate ammonia-lyase from Salmonella typhimurium. Purification and characterization of the crystalline enzyme, and sequence determination of the pyridoxal 5'-phosphate binding peptide. J Biol Chem. 1988 Jan 15;263(2):958-64 PMID:3275662
- ↑ Deka G, Bisht S, Savithri HS, Murthy MRN. Comparative structural and enzymatic studies on Salmonella typhimurium diaminopropionate ammonia lyase reveal its unique features. J Struct Biol. 2017 Dec 30. pii: S1047-8477(17)30235-6. doi:, 10.1016/j.jsb.2017.12.012. PMID:29294403 doi:http://dx.doi.org/10.1016/j.jsb.2017.12.012
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