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[[Image:3dap.gif|left|200px]]<br />
<applet load="3dap" size="450" color="white" frame="true" align="right" spinBox="true"
caption="3dap, resolution 2.2&Aring;" />
'''C. GLUTAMICUM DAP DEHYDROGENASE IN COMPLEX WITH NADP+ AND THE INHIBITOR 5S-ISOXAZOLINE'''<br />


==Overview==
==C. GLUTAMICUM DAP DEHYDROGENASE IN COMPLEX WITH NADP+ AND THE INHIBITOR 5S-ISOXAZOLINE==
The three-dimensional structures of Corynebacterium glutamicum, diaminopimelate dehydrogenase as a binary complex with the substrate, meso-diaminopimelate (meso-DAP) and a ternary complex with NADP+ and an, isoxazoline inhibitor [Abbot, S.D., Lane-Bell, P., Kanwar, P.S.S., and, Vederas, J. C. (1994) J. Am. Chem. Soc. 116, 6513-6520] have been solved, and refined against X-ray diffraction data to 2.2 A. Diaminopimelate, dehydrogenase is a homodimer of approximately 35,000 molecular weight, subunits and is the only dehydrogenase present in the bacterial, diaminopimelate/lysine biosynthetic pathway. Inhibitors of the enzymes of, L-lysine biosynthesis have been proposed as potential antibiotics or, herbicides, since mammals lack this metabolic pathway. Diaminopimelate, dehydrogenase catalyzes the unique, reversible, pyridine, dinucleotide-dependent oxidative deamination of the D-amino acid, stereocenter of meso-diaminopimelate to generate L-2-amino-6-oxopimelate., The enzyme is absolutely specific for the meso stereoisomer of DAP and, must distinguish between two opposite chiral amino acid centers on the, same symmetric substrate. The determination of the three-dimensional, structure of the enzyme--meso-diaminopimelate complex allows a description, of the molecular basis of this stereospecific discrimination. The, substrate is bound in an elongated cavity, in which the distribution of, residues that act as hydrogen bond donors or acceptors defines a single, orientation in which the substrate may bind in order to position the, D-amino acid center of meso-DAP near the oxidized nucleotide. The, previously described isoxazoline inhibitor binds at the same site as DAP, but has its L-amino acid center positioned where the D-amino acid center, of meso-DAP would normally be located, thereby generating a nonproductive, inhibitor complex. The relative positions of the N-terminal dinucleotide, and C-terminal substrate-binding domains in the diaminopimelate, dehydrogenase--NADP+, diaminopimelate dehydrogenase--DAP, and, diaminopimelate dehydrogenase--NADP(+)--inhibitor complexes confirm our, previous observations that the enzyme undergoes significant conformational, changes upon binding of both dinucleotide and substrate.
<StructureSection load='3dap' size='340' side='right'caption='[[3dap]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[3dap]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Corynebacterium_glutamicum Corynebacterium glutamicum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DAP FirstGlance]. <br>
3DAP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Corynebacterium_glutamicum Corynebacterium glutamicum] with NDP and DA3 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Diaminopimelate_dehydrogenase Diaminopimelate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.1.16 1.4.1.16] Structure known Active Sites: INH, N1 and N2. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=3DAP OCA].  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DA3:(2S,5,S)-2-AMINO-3-(3-CARBOXY-2-ISOXAZOLIN-5-YL)PROPANOIC+ACID'>DA3</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
==Reference==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3dap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dap OCA], [https://pdbe.org/3dap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dap RCSB], [https://www.ebi.ac.uk/pdbsum/3dap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dap ProSAT]</span></td></tr>
Substrate and inhibitor binding sites in Corynebacterium glutamicum diaminopimelate dehydrogenase., Scapin G, Cirilli M, Reddy SG, Gao Y, Vederas JC, Blanchard JS, Biochemistry. 1998 Mar 10;37(10):3278-85. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9521647 9521647]
</table>
== Function ==
[https://www.uniprot.org/uniprot/DAPDH_CORGL DAPDH_CORGL] Catalyzes the reversible NADPH-dependent reductive amination of L-2-amino-6-oxopimelate, the acyclic form of L-tetrahydrodipicolinate, to generate the meso compound, D,L-2,6-diaminopimelate. Probably plays a role in lysine biosynthesis. Exhibits a high substrate specificity for meso-2,6-diaminopimelate, since L,L-2,6-diaminopimelate, D,D-2,6-diaminopimelate, L-glutamate, L-alanine, L-leucine, L-valine, L-aspartate, L-threonine, L-homoserine, L-methionine, L-lysine, L-serine, L-phenylalanine, L-tyrosine, L-tryptophan, L-ornithine, L-histidine, L-arginine, D-glutamate, and D-alanine are not substrates for the oxidative deamination reaction. Can use NAD(+) only poorly since the activity observed in the presence of NAD(+) is about 3% of that with NADP(+).<ref>PMID:8865347</ref> <ref>PMID:8865347</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/da/3dap_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3dap ConSurf].
<div style="clear:both"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Corynebacterium glutamicum]]
[[Category: Corynebacterium glutamicum]]
[[Category: Diaminopimelate dehydrogenase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Blanchard JS]]
[[Category: Blanchard, J.S.]]
[[Category: Cirilli M]]
[[Category: Cirilli, M.]]
[[Category: Gao Y]]
[[Category: Gao, Y.]]
[[Category: Reddy SG]]
[[Category: Reddy, S.G.]]
[[Category: Scapin G]]
[[Category: Scapin, G.]]
[[Category: Vederas JC]]
[[Category: Vederas, J.C.]]
[[Category: DA3]]
[[Category: NDP]]
[[Category: asymmetric dimer]]
[[Category: d-amino acid dehydrogenase]]
[[Category: dehydrogenase]]
[[Category: inhibitor]]
[[Category: lysine biosynthesis]]
[[Category: nadp]]
[[Category: oxidoreductase]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov  5 18:46:15 2007''

Latest revision as of 12:40, 21 February 2024

C. GLUTAMICUM DAP DEHYDROGENASE IN COMPLEX WITH NADP+ AND THE INHIBITOR 5S-ISOXAZOLINEC. GLUTAMICUM DAP DEHYDROGENASE IN COMPLEX WITH NADP+ AND THE INHIBITOR 5S-ISOXAZOLINE

Structural highlights

3dap is a 2 chain structure with sequence from Corynebacterium glutamicum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DAPDH_CORGL Catalyzes the reversible NADPH-dependent reductive amination of L-2-amino-6-oxopimelate, the acyclic form of L-tetrahydrodipicolinate, to generate the meso compound, D,L-2,6-diaminopimelate. Probably plays a role in lysine biosynthesis. Exhibits a high substrate specificity for meso-2,6-diaminopimelate, since L,L-2,6-diaminopimelate, D,D-2,6-diaminopimelate, L-glutamate, L-alanine, L-leucine, L-valine, L-aspartate, L-threonine, L-homoserine, L-methionine, L-lysine, L-serine, L-phenylalanine, L-tyrosine, L-tryptophan, L-ornithine, L-histidine, L-arginine, D-glutamate, and D-alanine are not substrates for the oxidative deamination reaction. Can use NAD(+) only poorly since the activity observed in the presence of NAD(+) is about 3% of that with NADP(+).[1] [2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

  1. ↑ Reddy SG, Scapin G, Blanchard JS. Expression, purification, and crystallization of meso-diaminopimelate dehydrogenase from Corynebacterium glutamicum. Proteins. 1996 Aug;25(4):514-6. PMID:8865347 doi:http://dx.doi.org/10.1002/prot.12
  2. ↑ Reddy SG, Scapin G, Blanchard JS. Expression, purification, and crystallization of meso-diaminopimelate dehydrogenase from Corynebacterium glutamicum. Proteins. 1996 Aug;25(4):514-6. PMID:8865347 doi:http://dx.doi.org/10.1002/prot.12

3dap, resolution 2.20Å

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