Rhea - reaction knowledgebase

Enzymes

UniProtKB ^help_outline	5,402 proteins
Enzyme class ^help_outline	EC 1.21.98.4 PqqA peptide cyclase

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Name^help_outline [PQQ precursor protein] Identifier RHEA-COMP:14800 Reactive part ^help_outline
- Name ^help_outline EXXXY peptide Identifier CHEBI:141026 Charge -1 Formula C20H21N5O8R3 SMILES^help_outline *N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(*)=O)CC=1C=CC(=CC1)O)=O)*)=O)*)=O)*)=O)CCC([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Search links Involved in 1 reaction(s) Find proteins in UniProtKB for this molecule
Name ^help_outline S-adenosyl-L-methionine Identifier CHEBI:59789 Charge 1 Formula C15H23N6O5S InChIKey^help_outline MEFKEPWMEQBLKI-AIRLBKTGSA-O SMILES^help_outline C[S+](CC[C@H]([NH3+])C([O-])=O)C[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1cnc2c(N)ncnc12 2D coordinates Mol file for the small molecule Search links Involved in 842 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline 5'-deoxyadenosine Identifier CHEBI:17319 (CAS: 4754-39-6) ^help_outline Charge 0 Formula C10H13N5O3 InChIKey^help_outline XGYIMTFOTBMPFP-KQYNXXCUSA-N SMILES^help_outline C[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1cnc2c(N)ncnc12 2D coordinates Mol file for the small molecule Search links Involved in 66 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name^help_outline E-Y cross-linked-[PQQ precursor protein] Identifier RHEA-COMP:14801 Reactive part ^help_outline
- Name ^help_outline E-Y cross-linked EXXXY peptide Identifier CHEBI:141027 Charge -1 Formula C20H19N5O8R3 SMILES^help_outline *N[C@@H]1C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(*)=O)CC=2C=CC(=C(C2)C(C1)C([O-])=O)O)=O)*)=O)*)=O)*)=O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Search links Involved in 1 reaction(s) Find proteins in UniProtKB for this molecule
Name ^help_outline H⁺ Identifier CHEBI:15378 Charge 1 Formula H InChIKey^help_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILES^help_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Name ^help_outline L-methionine Identifier CHEBI:57844 Charge 0 Formula C5H11NO2S InChIKey^help_outline FFEARJCKVFRZRR-BYPYZUCNSA-N SMILES^help_outline CSCC[C@H]([NH3+])C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 118 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule

Cross-references

	RHEA:56836	RHEA:56837	RHEA:56838	RHEA:56839
Reaction direction	undefined	left-to-right	right-to-left	bidirectional
UniProtKB ^help_outline	5,402 proteins
EC numbers ^help_outline	1.21.98.4
MetaCyc ^help_outline		RXN-11176

Publications

Interaction of PqqE and PqqD in the pyrroloquinoline quinone (PQQ) biosynthetic pathway links PqqD to the radical SAM superfamily.

Wecksler S.R., Stoll S., Iavarone A.T., Imsand E.M., Tran H., Britt R.D., Klinman J.P.

pqqD is one of six genes required for PQQ production in Klebsiella pneumoniae. Herein, we demonstrate that PqqD interacts specifically with the radical SAM enzyme PqqE, causing a perturbation in the electronic environment around the [4Fe-4S](+) clusters. This interaction redirects the role for Pqq ... >> More

pqqD is one of six genes required for PQQ production in Klebsiella pneumoniae. Herein, we demonstrate that PqqD interacts specifically with the radical SAM enzyme PqqE, causing a perturbation in the electronic environment around the [4Fe-4S](+) clusters. This interaction redirects the role for PqqD in PQQ biosynthesis. << Less

Chem. Commun. (Camb.) 46:7031-7033(2010) [PubMed] [EuropePMC]
PqqD is a novel peptide chaperone that forms a ternary complex with the radical S-adenosylmethionine protein PqqE in the pyrroloquinoline quinone biosynthetic pathway.

Latham J.A., Iavarone A.T., Barr I., Juthani P.V., Klinman J.P.

Pyrroloquinoline quinone (PQQ) is a product of a ribosomally synthesized and post-translationally modified pathway consisting of five conserved genes, pqqA-E. PqqE is a radical S-adenosylmethionine (RS) protein with a C-terminal SPASM domain, and is proposed to catalyze the formation of a carbon-c ... >> More

Pyrroloquinoline quinone (PQQ) is a product of a ribosomally synthesized and post-translationally modified pathway consisting of five conserved genes, pqqA-E. PqqE is a radical S-adenosylmethionine (RS) protein with a C-terminal SPASM domain, and is proposed to catalyze the formation of a carbon-carbon bond between the glutamate and tyrosine side chains of the peptide substrate PqqA. PqqD is a 10-kDa protein with an unknown function, but is essential for PQQ production. Recently, in Klebsiella pneumoniae (Kp), PqqD and PqqE were shown to interact; however, the stoichiometry and KD were not obtained. Here, we show that the PqqE and PqqD interaction transcends species, also occurring in Methylobacterium extorquens AM1 (Me). The stoichiometry of the MePqqD and MePqqE interaction is 1:1 and the KD, determined by surface plasmon resonance spectroscopy (SPR), was found to be ∼12 μm. Moreover, using SPR and isothermal calorimetry techniques, we establish for the first time that MePqqD binds MePqqA tightly (KD ∼200 nm). The formation of a ternary MePqqA-D-E complex was captured by native mass spectrometry and the KD for the MePqqAD-MePqqE interaction was found to be ∼5 μm. Finally, using a bioinformatic analysis, we found that PqqD orthologues are associated with the RS-SPASM family of proteins (subtilosin, pyrroloquinoline quinone, anaerobic sulfatase maturating enzyme, and mycofactocin), all of which modify either peptides or proteins. In conclusion, we propose that PqqD is a novel peptide chaperone and that PqqD orthologues may play a similar role in peptide modification pathways that use an RS-SPASM protein. << Less

J. Biol. Chem. 290:12908-12918(2015) [PubMed] [EuropePMC]
Demonstration that the radical S-adenosylmethionine (SAM) enzyme PqqE catalyzes de novo carbon-carbon cross-linking within a peptide substrate PqqA in the presence of the peptide chaperone PqqD.

Barr I., Latham J.A., Iavarone A.T., Chantarojsiri T., Hwang J.D., Klinman J.P.

The radical S-adenosylmethionine (SAM) protein PqqE is predicted to function in the pyrroloquinoline quinone (PQQ) biosynthetic pathway via catalysis of carbon-carbon bond formation between a glutamate and tyrosine side chain within the small peptide substrate PqqA. We report here that PqqE activi ... >> More

The radical S-adenosylmethionine (SAM) protein PqqE is predicted to function in the pyrroloquinoline quinone (PQQ) biosynthetic pathway via catalysis of carbon-carbon bond formation between a glutamate and tyrosine side chain within the small peptide substrate PqqA. We report here that PqqE activity is dependent on the accessory protein PqqD, which was recently shown to bind PqqA tightly. In addition, PqqE activity in vitro requires the presence of a flavodoxin- and flavodoxin reductase-based reduction system, with other reductants leading to an uncoupled cleavage of the co-substrate SAM. These results indicate that PqqE, in conjunction with PqqD, carries out the first step in PQQ biosynthesis: a radical-mediated formation of a new carbon-carbon bond between two amino acid side chains on PqqA. << Less

J. Biol. Chem. 291:8877-8884(2016) [PubMed] [EuropePMC]

RHEA:56836 [PQQ precursor protein] + S-adenosyl-L-methionine = 5'-deoxyadenosine + E-Y cross-linked-[PQQ precursor protein] + H(+) + L-methionine

Enzymes

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Cross-references

Publications

Interaction of PqqE and PqqD in the pyrroloquinoline quinone (PQQ) biosynthetic pathway links PqqD to the radical SAM superfamily.

PqqD is a novel peptide chaperone that forms a ternary complex with the radical S-adenosylmethionine protein PqqE in the pyrroloquinoline quinone biosynthetic pathway.

Demonstration that the radical S-adenosylmethionine (SAM) enzyme PqqE catalyzes de novo carbon-carbon cross-linking within a peptide substrate PqqA in the presence of the peptide chaperone PqqD.