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Catalytic Site Atlas

CSA LITERATURE entry for 1ujn

E.C. name3-dehydroquinate synthase
SpeciesThermus thermophilus (Bacteria)
E.C. Number (IntEnz) 4.2.3.4
CSA Homologues of 1ujn
CSA Entries With UniProtID
CSA Entries With EC Number 4.2.3.4
PDBe Entry 1ujn
PDBSum Entry 1ujn
MACiE Entry 1ujn

Literature Report

IntroductionDehydroquinate synthase (DHQS), isolated from Thermus thermophilus, catalyses the NAD+- and Zn(II)-dependent conversion of 3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate (DHAP) to dehydroquinate and phosphate. This reaction is part of the shikimate pathway that generates aromatic amino acids in bacteria, plants and microbial eukaryotes. As such it is a potential antibacterial and antifungal drug target.
MechansimHis235 deprotonates a water molecule, which in turn deprotonates the C5 hydroxyl of DHAP. In concert, the C5 oxygen forms a carbonyl and the C5 hydride is transferred to the C4 position of NAD+. A Zn(II) ion facilitates this step by polarising the hydroxyl group and stabilising the transition state. The phosphate of the intermediate removes the C6 proton, leading to the beta-elimination of the phosphate group. NADH transfers a hydride to the C5 position and the developing alkoxide is protonated by a water molecule, which is in turn protonated by His235. Zn(II) facilitates this reaction by polarising the carbonyl and stabilising the transient negative charge on the oxygen. Glu220 deprotonates a different water molecule and the resulting hydroxide deprotonates the C2 hydroxyl. The alkoxide forms a carbonyl and the C2-O1 bond is cleaved, opening the ring. There is then rotation around the C5-C6 bond and an intramolecular aldol condensation reaction closes the ring. The developing alkoxide is protonated by water, which is turn protonated by Glu220, to form dehydroquinate.
Reaction

Catalytic Sites for 1ujn

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
ArgA224224macie:sideChainArg224 coordinates to the carboxylate during ring opening and in doing so helps to prevent epimerisation at the C2 position.
AsnA228228macie:sideChainAsn228 is potentially involved in the beta-elimination of the phosphate by stabilising the transition state and/or forcing the phosphate to adopt the correct position for C6 proton abstraction.
LysA131131macie:sideChainLys13 is potentially involved in the beta-elimination of the phosphate by stabilising the transition state and/or forcing the phosphate to adopt the correct position for C6 proton abstraction. It coordinates the carboxylate during ring opening and in doing so helps to prevent epimerisation at the C2 position. Lys131 also stabilises the negative charge formed upon ring opening. This could either be by electrostatic interactions or by protonating the oxygen to form an enol.
GluA220220macie:sideChainGlu220 is part of a proton shuffling system. It deprotonates water during ring opening and protonates water during ring closing.
LysA210210macie:sideChainLys210 coordinates to the carboxylate during ring opening and in doing so helps to prevent epimerisation at the C2 position.
HisA235235macie:sideChainHis235 is part of a proton shuffling system. It deprotonates water during DHAP oxidation and protonates water during the reduction of the intermediate. It is also potentially involved in the beta-elimination of the phosphate by stabilising the transition state and/or forcing the phosphate to adopt the correct position for C6 proton abstraction.
ArgB109109macie:sideChainArg130 is potentially involved in the beta-elimination of the phosphate by stabilising the transition state and/or forcing the phosphate to adopt the correct position for C6 proton abstraction.

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
ArgB224224macie:sideChainError
AsnB228228macie:sideChainError
LysB131131macie:sideChainError
GluB220220macie:sideChainError
LysB210210macie:sideChainError
HisB235235macie:sideChainError

Annotated By Reference To The Literature - Site 5 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
ArgA224224macie:sideChainArg224 coordinates to the carboxylate during ring opening and in doing so helps to prevent epimerisation at the C2 position.
AsnA228228macie:sideChainAsn228 is potentially involved in the beta-elimination of the phosphate by stabilising the transition state and/or forcing the phosphate to adopt the correct position for C6 proton abstraction.
LysA131131macie:sideChainLys13 is potentially involved in the beta-elimination of the phosphate by stabilising the transition state and/or forcing the phosphate to adopt the correct position for C6 proton abstraction. It coordinates the carboxylate during ring opening and in doing so helps to prevent epimerisation at the C2 position. Lys131 also stabilises the negative charge formed upon ring opening. This could either be by electrostatic interactions or by protonating the oxygen to form an enol.
GluA220220macie:sideChainGlu220 is part of a proton shuffling system. It deprotonates water during ring opening and protonates water during ring closing.
LysA210210macie:sideChainLys210 coordinates to the carboxylate during ring opening and in doing so helps to prevent epimerisation at the C2 position.
HisA235235macie:sideChainHis235 is part of a proton shuffling system. It deprotonates water during DHAP oxidation and protonates water during the reduction of the intermediate. It is also potentially involved in the beta-elimination of the phosphate by stabilising the transition state and/or forcing the phosphate to adopt the correct position for C6 proton abstraction.
ArgB109109macie:sideChainArg130 is potentially involved in the beta-elimination of the phosphate by stabilising the transition state and/or forcing the phosphate to adopt the correct position for C6 proton abstraction.

Annotated By Reference To The Literature - Site 6 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
ArgA109109macie:sideChainError

Literature References

Notes:Catalytic residues have been determined through sequence alignment with DHQS from Aspergillus nidulans. The catalytic residue Arg259 from A. nidulans is Leu219 in T. thermophilus and so has been left out. Lys356 of A. nidulans does not have a corresponding residue in T. thermophilus. Lys356 is thought to be involved in transition state stabilisation during the beta-elimination of the phosphate. Much of this article is based on a paper (9685163) that claims that the basic residue in A. nidulans is Arg260. There is no Arg260, but there are Arg259 and Glue260. Examination of the crystal structure and the use of another paper (12614613) leads to the conclusion that the correct residue in A. nidulans is Glu260. Therefore the residue in T. thermophilus is Glu220.
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