Any feedback?
Please rate this page
(enzyme.php)
(0/150)

BRENDA support

BRENDA Home
show all | hide all No of entries

Information on EC 3.6.4.10 - non-chaperonin molecular chaperone ATPase

for references in articles please use BRENDA:EC3.6.4.10
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
IUBMB Comments
This is a highly diverse group of enzymes that perform many functions that are similar to those of chaperonins. They comprise a number of heat-shock-cognate proteins. They are also active in clathrin uncoating and in the oligomerization of actin.
Specify your search results
Select one or more organisms in this record: ?
This record set is specific for:
UNIPROT: P63284
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)
Word Map
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
Synonyms
hsp90, heat shock protein, grp78, hsp60, groel, molecular chaperone, heat shock protein 70, hsc70, heat shock protein 90, hsp40, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ClpB disaggregase
-
molecular chaperone Hsc70 ATPase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (polypeptide-polymerizing)
This is a highly diverse group of enzymes that perform many functions that are similar to those of chaperonins. They comprise a number of heat-shock-cognate proteins. They are also active in clathrin uncoating and in the oligomerization of actin.
CAS REGISTRY NUMBER
COMMENTARY hide
9000-83-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + H2O
ADP + phosphate
show the reaction diagram
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + H2O
ADP + phosphate
show the reaction diagram
-
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
coiled-coil M-domains repress ClpB activity by encircling the AAA1 ring
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
mechanism of ClpB activation by comparing ATPase mechanisms and cryo-EM structures of ClpB wild-type and a constitutively active ClpB M-domain mutant. ClpB activation requires two signals: (1) interaction with the Hsp70 partner chaperone and (2) binding to substrate protein
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
cooperative mode of ATP hydrolysis
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
substrate-triggered decrease in cooperativity of mutant ClpB-K476C ATPase activity. The K476C mutation weakens the dynamic interaction between M-domain and AAA1 ring resulting in M-domain dissociation and persistent, Hsp70-independent derepression of ClpB ATPase activity. Consequently, the ATPase activation by substrate is much stronger than in wild-type ClpB, and mutant ClpB-K476C has increased protein disaggregation activity, linked to its ability to unfold stable domains, an activity not observed for wild-type ClpB. ATP concentrations at half-maximal ATP hydrolysis rates of ClpB-K476C drop to 1.4 mM in the presence of substrate, compared with 4.3 mM for wild-type ClpB in the presence of substrate indicating that only the fully two-step activated state of ClpB reaches high ATPase activity at physiological ATP concentrations, which coincides with decreased cooperativity. Substrate-bound ClpB-K476C structures reveal large displacements of AAA2 pore loops. Comparisons of substrate binding structures of wild-type and mutant enzymes, overview
additional information
disaggregase ClpB contains tandem ATPase domains (AAA1, AAA2) and shifts between low and high ATPase and threading activities. Coiled-coil M-domains repress ClpB activity by encircling the AAA1 ring. ClpB activation reduces ATPase cooperativity and induces a sequential mode of ATP hydrolysis in the AAA2 ring, the main ATPase motor. AAA1 and AAA2 rings do not work synchronously but in alternating cycles. This ensures high grip, enabling substrate threading via a processive, rope-climbing mechanism. Residue Lys476 is part of a conserved salt bridge network that regulates the dynamic interaction between M-domain and AAA1 ring. Comparisons of substrate binding structures of wild-type and mutant enzymes, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CLPB_ECOLI
Escherichia coli (strain K12)
857
0
95585
Swiss-Prot
-
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E279A/K476C/E678A
site-directed mutagenesis, the mutant shows a reduced number of subunits
K476C
site-directed mutagenesis, the mutation weakens the dynamic interaction between M-domain and AAA1 ring resulting in M-domain dissociation and persistent, Hsp70-independent derepression of ClpB ATPase activity. Consequently, the ATPase activation by substrate is much stronger than in wild-type ClpB, and mutant ClpB-K476C has increased protein disaggregation activity, linked to its ability to unfold stable domains, an activity not observed for wild-type ClpB. ATP concentrations at half-maximal ATP hydrolysis rates of ClpB-K476C drop to 1.4 mM in the presence of substrate, compared with 4.3 mM for wild-type ClpB in the presence of substrate indicating that only the fully two-step activated state of ClpB reaches high ATPase activity at physiological ATP concentrations, which coincides with decreased cooperativity. Substrate-bound ClpB-K476C structures reveal large displacements of AAA2 pore loops
Y251A/K476C
site-directed mutagenesis, the mutant shows altered kinetics and reduced activity compared to wild-type enzyme
Y251A/K476C/Y653A
site-directed mutagenesis, the mutant shows altered kinetics and reduced activity compared to wild-type enzyme
Y653A/K476C
site-directed mutagenesis, the mutant shows altered kinetics and reduced activity compared to wild-type enzyme
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Deville, C.; Franke, K.; Mogk, A.; Bukau, B.; Saibil, H.R.
Two-step activation mechanism of the ClpB disaggregase for sequential substrate threading by the main ATPase motor
Cell Rep.
27
3433-3446.e4
2019
Escherichia coli (P63284)
Manually annotated by BRENDA team
Rotanova, T.V.; Andrianova, A.G.; Kudzhaev, A.M.; Li, M.; Botos, I.; Wlodawer, A.; Gustchina, A.
New insights into structural and functional relationships between LonA proteases and ClpB chaperones
FEBS Open Bio
9
1536-1551
2019
Escherichia coli (P63284), Thermus thermophilus (Q9RA63)
Manually annotated by BRENDA team