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[[Image:1f06.gif|left|200px]]<br /><applet load="1f06" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1f06, resolution 2.1&Aring;" />
'''THREE DIMENSIONAL STRUCTURE OF THE TERNARY COMPLEX OF CORYNEBACTERIUM GLUTAMICUM DIAMINOPIMELATE DEHYDROGENASE NADPH-L-2-AMINO-6-METHYLENE-PIMELATE'''<br />


==Overview==
==THREE DIMENSIONAL STRUCTURE OF THE TERNARY COMPLEX OF CORYNEBACTERIUM GLUTAMICUM DIAMINOPIMELATE DEHYDROGENASE NADPH-L-2-AMINO-6-METHYLENE-PIMELATE==
The three-dimensional (3D) structure of Corynebacterium glutamicum diaminopimelate D-dehydrogenase in a ternary complex with NADPH and L-2-amino-6-methylene-pimelate has been solved and refined to a resolution of 2.1 A. L-2-Amino-6-methylene-pimelate was recently synthesized and shown to be a potent competitive inhibitor (5 microM) vs. meso-diaminopimelate of the Bacillus sphaericus dehydrogenase (Sutherland et al., 1999). Diaminopimelate dehydrogenase catalyzes the reversible NADP+ -dependent oxidation of the D-amino acid stereocenter of mesodiaminopimelate, and is the only enzyme known to catalyze the oxidative deamination of a D-amino acid. The enzyme is involved in the biosynthesis of meso-diaminopimelate and L-lysine from L-aspartate, a biosynthetic pathway of considerable interest because it is essential for growth of certain bacteria. The dehydrogenase is found in a limited number of species of bacteria, as opposed to the alternative succinylase and acetylase pathways that are widely distributed in bacteria and plants. The structure of the ternary complex reported here provides a structural rationale for the nature and potency of the inhibition exhibited by the unsaturated L-2-amino-6-methylene-pimelate against the dehydrogenase. In particular, we compare the present structure with other structures containing either bound substrate, meso-diaminopimelate, or a conformationally restricted isoxazoline inhibitor. We have identified a significant interaction between the alpha-L-amino group of the unsaturated inhibitor and the indole ring of Trp144 that may account for the tight binding of this inhibitor.
<StructureSection load='1f06' size='340' side='right'caption='[[1f06]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[1f06]] 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=1F06 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F06 FirstGlance]. <br>
1F06 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 <scene name='pdbligand=NDP:'>NDP</scene> and <scene name='pdbligand=2NP:'>2NP</scene> 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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F06 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]] 2.1&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2NP:L-2-AMINO-6-METHYLENE-PIMELIC+ACID'>2NP</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=1f06 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f06 OCA], [https://pdbe.org/1f06 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f06 RCSB], [https://www.ebi.ac.uk/pdbsum/1f06 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f06 ProSAT]</span></td></tr>
The three-dimensional structure of the ternary complex of Corynebacterium glutamicum diaminopimelate dehydrogenase-NADPH-L-2-amino-6-methylene-pimelate., Cirilli M, Scapin G, Sutherland A, Vederas JC, Blanchard JS, Protein Sci. 2000 Oct;9(10):2034-7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11106178 11106178]
</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/f0/1f06_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=1f06 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: Caplan JF]]
[[Category: Caplan, J F.]]
[[Category: Cirilli M]]
[[Category: Cirilli, M.]]
[[Category: Scapin G]]
[[Category: Scapin, G.]]
[[Category: Sutherland A]]
[[Category: Sutherland, A.]]
[[Category: Vederas JC]]
[[Category: Vederas, J C.]]
[[Category: 2NP]]
[[Category: NDP]]
[[Category: enzyme-nadph-inhibitor ternary complex]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:33:24 2008''

Latest revision as of 10:09, 7 February 2024

THREE DIMENSIONAL STRUCTURE OF THE TERNARY COMPLEX OF CORYNEBACTERIUM GLUTAMICUM DIAMINOPIMELATE DEHYDROGENASE NADPH-L-2-AMINO-6-METHYLENE-PIMELATETHREE DIMENSIONAL STRUCTURE OF THE TERNARY COMPLEX OF CORYNEBACTERIUM GLUTAMICUM DIAMINOPIMELATE DEHYDROGENASE NADPH-L-2-AMINO-6-METHYLENE-PIMELATE

Structural highlights

1f06 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 2.1Å
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

1f06, resolution 2.10Å

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