Three-subunit bacterial urease biogenesis and urea hydrolysis

A reusable bacterial module in which UreA, UreB, and UreC assemble the urease apoprotein, UreD, UreE, UreF, and UreG install the carbamylated dinickel metallocenter in a GTP-dependent activation process, and the mature urease complex hydrolyzes urea. The module covers the common three-chain bacterial UreABC implementation and its UreDEFG maturation system. It does not include general nickel uptake or homeostasis, urea transport, regulation of urease expression, or downstream assimilation of released ammonia.

MODULE:urease_biogenesis_urea_hydrolysisDRAFTCONCRETEBiological Processmodules/urease_biogenesis_urea_hydrolysis.yaml
urea catabolic processGO:0043419
PMID:7909161
In vitro activation of urease apoprotein and role of UreD as a chaperone required for nickel metallocenter assembly
Establishes the UreABC apoprotein and the requirement for UreD, UreE, UreF, and UreG in functional metallocenter assembly.
The formation of active urease in Klebsiella aerogenes requires the presence of three structural genes for the apoprotein (ureA, ureB, and ureC), as well as four accessory genes (ureD, ureE, ureF, and ureG) that are involved in functional assembly of the metallocenter in this nickel-containing enzyme.
PMID:10500143
GTP-dependent activation of urease apoprotein in complex with the UreD, UreF, and UreG accessory proteins
Establishes that UreG-dependent GTP hydrolysis activates the UreD-UreF-UreG-apourease complex at physiological bicarbonate.
Based on studies involving a nonhydrolyzable analog of GTP, we conclude that nucleotide hydrolysis, not just binding, is required for this process.
PMID:8318889
Purification and characterization of Klebsiella aerogenes UreE protein - a nickel-binding protein that functions in urease metallocenter assembly
Establishes UreE as a cytoplasmic nickel-binding donor for urease maturation.
We hypothesize that UreE binds intracellular nickel ion and functions as a nickel donor during metallocenter assembly into the urease apoprotein.

Exact PSEPK representatives ground the reusable roles without making the module species-restricted. General nickel import and ammonia assimilation are inputs and consequences, respectively, rather than module parts.

6Nodes
5Parts
0Variant Sets
0Variants
6Annotons
3Connections

Derived QC

Recommended-field compliance

60.0% recommended fields populated
  • knowledge_gaps[0] · status (0/1)
  • knowledge_gaps[0] · provenance (0/1)

Module deep research

✗ none found

No MODULE:urease_biogenesis_urea_hydrolysis deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (7/7 grounded genes reviewed)

7 complete review(s) · 1 with deep research · 0 missing review · 6 reviewed but lacking deep research

Gene Review Complete Deep research
ureA Q88J06 ✓ ✓ ✗
ureB Q88J05 ✓ ✓ ✗
ureC Q88J04 ✓ ✓ ✗
ureD Q88J07 ✓ ✓ ✗
ureE Q88J03 ✓ ✓ ✗
ureF Q88J01 ✓ ✓ ✓
ureG Q88J00 ✓ ✓ ✗

Details

Three-subunit bacterial urease biogenesis and urea hydrolysisBiological Processurease_biogenesis_urea_hydrolysis

Assembly of a UreABC apoprotein, UreDEFG-dependent dinickel-site activation, and hydrolysis of urea by the mature complex.

urea catabolic processGO:0043419

Connections

The assembled UreABC apoprotein is the client of the UreDEFG activation machinery.
Carbamylation and dinickel-site assembly convert apo-urease into the catalytically competent complex.
Part 1: apo-urease structural complex assembly
Apo-urease structural complex assemblyCellular Componentapo_urease_assembly

UreA, UreB, and UreC associate into the inactive three-subunit urease apoprotein before nickel insertion.

Annotons

Three-subunit bacterial apo-urease complex
apo_urease_complex
Participant: Protein Complex: three-subunit bacterial apo-urease complex
Protein Complex:
three-subunit bacterial apo-urease complexGO:0035550 Inactive UreABC complex lacking the carbamylated dinickel active site; the GO complex term names both apo and mature structural assemblies.
Active units:
UreA gamma structural subunit
Participant: Family: bacterial UreA gamma-subunit family
Family:
bacterial UreA gamma-subunit familyInterPro:IPR002026
Representative Members: PSEPK UreA exemplarUniProtKB:Q88J06
Role: Structural gamma chain that contributes to the assembled complex but does not independently catalyze urea hydrolysis.
file:PSEPK/ureA/ureA-uniprot.txt
Q88J06 is the reviewed UreA gamma subunit of the PSEPK heterotrimer.
UreB beta structural subunit
Participant: Family: bacterial UreB beta-subunit family
Family:
bacterial UreB beta-subunit familyInterPro:IPR002019
Representative Members: PSEPK UreB exemplarUniProtKB:Q88J05
Role: Structural beta chain that contributes to the assembled complex but does not independently catalyze urea hydrolysis.
file:PSEPK/ureB/ureB-uniprot.txt
Q88J05 is the reviewed UreB beta subunit of the PSEPK heterotrimer.
UreC alpha catalytic subunit
Participant: Family: bacterial UreC alpha-subunit family
Family:
bacterial UreC alpha-subunit familyPANTHER:PTHR43440:SF1
Representative Members: PSEPK UreC exemplarUniProtKB:Q88J04
Role: Catalytic alpha chain that supplies the carbamylated lysine and ligands of the dinickel active site after maturation.
PMID:8718850
Structural analysis places the binickel active center in the alpha subunit.
file:PSEPK/ureC/ureC-uniprot.txt
Q88J04 is the reviewed nickel-binding UreC alpha subunit of PSEPK urease.

Builds the preorganized UreABC apoprotein that is the client for UreDEFG-dependent metallocenter installation.

PMID:8718850
The apoenzyme retains the UreABC architecture but lacks carbamate and nickel at the active site.
With the exception of the active site, in which a water molecule takes the place of the missing carbamate and nickel atoms, the structure of the apoenzyme is nearly identical to that of the holoenzyme, suggesting a high degree of preorganization which helps explain the tight binding of nickel.
Part 2: nickel delivery and GTP-dependent urease activation
Nickel delivery and GTP-dependent urease activationBiological Processurease_metallocenter_activation

UreD, UreF, and UreG form an activation complex on apo-urease; UreE supplies nickel and UreG hydrolyzes GTP to support installation of the carbamylated dinickel center.

Connections

The UreD-UreF scaffold recruits and gates the UreE/UreG nickel-delivery machinery.
Part 1: activation-complex recruitment to apo-urease
UreD-UreF activation scaffold formationProtein Complexuredf_activation_scaffold

Annotons

UreD apo-urease maturation scaffold
ured_urease_scaffold
Participant: Family: bacterial UreD accessory-protein family
Family:
bacterial UreD accessory-protein familyPANTHER:PTHR33643:SF1
Representative Members: PSEPK UreD exemplarUniProtKB:Q88J07

Binds apo-urease and scaffolds recruitment of the other activation proteins.

PMID:7909161
UreD binds urease apoprotein and is required for nickel incorporation.
UreF activation-complex checkpoint
uref_activation_checkpoint
Participant: Family: bacterial UreF accessory-protein family
Family:
bacterial UreF accessory-protein familyPANTHER:PTHR33620:SF1
Representative Members: PSEPK UreF exemplarUniProtKB:Q88J01

Couples UreG recruitment and nucleotide turnover to productive rather than adventitious metal incorporation.

PMID:22369361
UreF interaction with UreG gates GTPase activity and maturation fidelity.
Part 2: nickel handoff and GTP hydrolysis
UreE-UreG nickel handoff and GTP hydrolysisBiological Processuree_ureg_nickel_handoff

Annotons

UreE nickel metallochaperone
uree_nickel_metallochaperone
Participant: Family: bacterial UreE nickel-metallochaperone family
Family:
bacterial UreE nickel-metallochaperone familyInterPro:IPR012406
Representative Members: PSEPK UreE exemplarUniProtKB:Q88J03

Function

nickel cation bindingGO:0016151

Binds cytoplasmic nickel and is proposed to supply it to the urease activation machinery.

PMID:8318889
Purified UreE binds nickel and was proposed to donate it during metallocenter assembly.
UreG GTPase metallochaperone
ureg_gtpase_metallochaperone
Participant: Family: bacterial UreG G3E GTPase family
Family:
bacterial UreG G3E GTPase familyPANTHER:PTHR31715:SF0
Representative Members: PSEPK UreG exemplarUniProtKB:Q88J00

Function

GTPase activityGO:0003924
Substrates: GTP water
Products: GDP phosphate

Uses GTP hydrolysis in the activation complex to couple nickel-site assembly to productive urease maturation.

PMID:10500143
A UreG nucleotide-site variant localized the GTP-hydrolysis requirement to UreG.
Part 3: urea hydrolysis by mature urease
Urea hydrolysis by mature ureaseReactionmature_urease_hydrolysis

Annotons

Mature dinickel urease activity
mature_urease_activity
Participant: Protein Complex: mature three-subunit bacterial urease complex
Protein Complex:
mature three-subunit bacterial urease complexGO:0035550
Active units:
UreA gamma subunit
Participant: Family: bacterial UreA gamma-subunit family
Family:
bacterial UreA gamma-subunit familyInterPro:IPR002026
Representative Members: PSEPK UreA exemplarUniProtKB:Q88J06
Role: Structural contributor to mature urease activity.
Function:
contributes to urease activityGO:0009039
UreB beta subunit
Participant: Family: bacterial UreB beta-subunit family
Family:
bacterial UreB beta-subunit familyInterPro:IPR002019
Representative Members: PSEPK UreB exemplarUniProtKB:Q88J05
Role: Structural contributor to mature urease activity.
Function:
contributes to urease activityGO:0009039
UreC alpha subunit
Participant: Family: bacterial UreC alpha-subunit family
Family:
bacterial UreC alpha-subunit familyPANTHER:PTHR43440:SF1
Representative Members: PSEPK UreC exemplarUniProtKB:Q88J04
Role: Supplies the carbamylated dinickel catalytic center.
Function:
enables urease activity as the catalytic subunitGO:0009039

Function

urease activityGO:0009039
Substrates: ureaCHEBI:16199 waterCHEBI:15377 waterCHEBI:15377 hydronCHEBI:15378
Products: hydrogencarbonateCHEBI:17544 ammoniumCHEBI:28938 ammoniumCHEBI:28938
Cofactors: two nickel(II) ions carbamylated active-site lysine

Processes

urea catabolic processGO:0043419

Hydrolyzes urea after UreDEFG-dependent metallocenter activation.

RHEA:20557
Urease reaction
Rhea 20557 defines the EC 3.5.1.5 urea hydrolysis reaction.
file:PSEPK/ureC/ureC-uniprot.txt
PSEPK UreC is reviewed as the nickel-binding alpha subunit of EC 3.5.1.5 urease.