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Catalytic Site Atlas

CSA LITERATURE entry for 1e5q

E.C. namesaccharopine dehydrogenase (NADP+, L-glutamate-forming)
SpeciesMagnaporthe grisea ()
E.C. Number (IntEnz) 1.5.1.10
CSA Homologues of 1e5qThere are 90 Homologs
CSA Entries With UniProtID Q9P4R4
CSA Entries With EC Number 1.5.1.10
PDBe Entry 1e5q
PDBSum Entry 1e5q
MACiE Entry 1e5q

Literature Report

IntroductionTwo lysine biosynthesis pathway: ubiquitous diaminopimelate pathway found in plants, bacteria and lower fungi. And the alpha-aminoadipate pathway(AAA pathway) found in higher fungi and cyanobacteria.
The AAA pathway synthesises lysine from alpha-ketoglutarate and it is a member of the glutamate family of amino acid biosynthetic pathways.
A number of fungi using this lysine synthesis pathway are human and plant pathogens. Selective inhibition of the essential biosynthetic pathway of lysine can be a possible means of controlling these pathogens.
Saccharopine reductase catalyses the penultimate step in the AAA pathway in which glutamate and alpha-aminoadipic-delta-semialdehyde are reversibly converted to saccharophine, using, in preference, NADPH as cofactor. But it can also utilise NADH though with low catalytic efficiency.
MechansimIn the forward reaction from glutamate and alpha-aminoadipic-delta-semialdehyde to saccharopine, first, the amino nitrogen atom of the glutamate acts as a nucleophile to attack the carbon atom of the aldehyde group of alpha-aminoadipate-delta-semialdehyde, resulting in the formation of carbinoamine. Second, elimination of a water molecule results in Schiff-base intermediate and finally, NADPH transfers hydrides to the intermediate to form saccharopine.
In the reverse reaction, the hydrolysis of the Schiff-base requires the nucleophilic attack of a water molecule on carbon C6 of saccharopine. Asp126 activates a water molecule to promote the hydrolysis.
Reaction

Catalytic Sites for 1e5q

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA126126macie:sideChainIt deprotonates a water molecule to allow its hydrolysis of the Schiff-base intermediate in the reverse reaction which saccharopine is converted back to glutamate and alpha-aminoadipic-delta-semialdehyde.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspB126126macie:sideChainIt deprotonates a water molecule to allow its hydrolysis of the Schiff-base intermediate in the reverse reaction which saccharopine is converted back to glutamate and alpha-aminoadipic-delta-semialdehyde.

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspC126126macie:sideChainIt deprotonates a water molecule to allow its hydrolysis of the Schiff-base intermediate in the reverse reaction which saccharopine is converted back to glutamate and alpha-aminoadipic-delta-semialdehyde.

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspD126126macie:sideChainIt deprotonates a water molecule to allow its hydrolysis of the Schiff-base intermediate in the reverse reaction which saccharopine is converted back to glutamate and alpha-aminoadipic-delta-semialdehyde.

Annotated By Reference To The Literature - Site 5 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspE126126macie:sideChainIt deprotonates a water molecule to allow its hydrolysis of the Schiff-base intermediate in the reverse reaction which saccharopine is converted back to glutamate and alpha-aminoadipic-delta-semialdehyde.

Annotated By Reference To The Literature - Site 6 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspF126126macie:sideChainIt deprotonates a water molecule to allow its hydrolysis of the Schiff-base intermediate in the reverse reaction which saccharopine is converted back to glutamate and alpha-aminoadipic-delta-semialdehyde.

Annotated By Reference To The Literature - Site 7 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspG126126macie:sideChainIt deprotonates a water molecule to allow its hydrolysis of the Schiff-base intermediate in the reverse reaction which saccharopine is converted back to glutamate and alpha-aminoadipic-delta-semialdehyde.

Annotated By Reference To The Literature - Site 8 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspH126126macie:sideChainIt deprotonates a water molecule to allow its hydrolysis of the Schiff-base intermediate in the reverse reaction which saccharopine is converted back to glutamate and alpha-aminoadipic-delta-semialdehyde.

Literature References

Notes:For the conversion from glutamate and alpha-aminoadipic-delta-semialdehyde to saccharopine, there is no catalytic residues directly involved. From PMID 11080625, it was suggested that there are no protein residue in the active site which might facilitates proton transfers, which are expected in the catalysis. And there are also no enzymatic group or helix dipoles that can provide stabilisation of the transition state of the nucleophilic attack.
Johansson E
Crystal structure of saccharopine reductase from Magnaporthe grisea, an enzyme of the alpha-aminoadipate pathway of lysine biosynthesis.
Structure 2000 8 1037-1047
PubMed: 11080625
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