Type |
Details |
Score |
Publication |
First Author: |
Hammar E |
Year: |
2009 |
Journal: |
Endocrinology |
Title: |
Role of the Rho-ROCK (Rho-associated kinase) signaling pathway in the regulation of pancreatic beta-cell function. |
Volume: |
150 |
Issue: |
5 |
Pages: |
2072-9 |
|
•
•
•
•
•
|
Publication |
First Author: |
Gancz D |
Year: |
2009 |
Journal: |
Mol Immunol |
Title: |
Involvement of the c-jun N-terminal kinases JNK1 and JNK2 in complement-mediated cell death. |
Volume: |
47 |
Issue: |
2-3 |
Pages: |
310-7 |
|
•
•
•
•
•
|
Publication |
First Author: |
Vallon M |
Year: |
2010 |
Journal: |
Exp Cell Res |
Title: |
Tumor endothelial marker 5 expression in endothelial cells during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of cell proliferation. |
Volume: |
316 |
Issue: |
3 |
Pages: |
412-21 |
|
•
•
•
•
•
|
Publication |
First Author: |
Ando S |
Year: |
2010 |
Journal: |
Biochem Biophys Res Commun |
Title: |
FTY720 exerts a survival advantage through the prevention of end-stage glomerular inflammation in lupus-prone BXSB mice. |
Volume: |
394 |
Issue: |
3 |
Pages: |
804-10 |
|
•
•
•
•
•
|
Publication |
First Author: |
Maekawa M |
Year: |
2010 |
Journal: |
J Neurochem |
Title: |
Analysis of strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia. |
Volume: |
115 |
Issue: |
6 |
Pages: |
1374-85 |
|
•
•
•
•
•
|
Publication |
First Author: |
Wu X |
Year: |
2010 |
Journal: |
Proc Natl Acad Sci U S A |
Title: |
Properdin homeostasis requires turnover of the alternative complement pathway. |
Volume: |
107 |
Issue: |
45 |
Pages: |
19444-8 |
|
•
•
•
•
•
|
Publication |
First Author: |
Civciristov S |
Year: |
2019 |
Journal: |
J Biol Chem |
Title: |
Ligand-dependent spatiotemporal signaling profiles of the μ-opioid receptor are controlled by distinct protein-interaction networks. |
Volume: |
294 |
Issue: |
44 |
Pages: |
16198-16213 |
|
•
•
•
•
•
|
Publication |
First Author: |
Ståhl AL |
Year: |
2011 |
Journal: |
Blood |
Title: |
Complement activation on platelet-leukocyte complexes and microparticles in enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome. |
Volume: |
117 |
Issue: |
20 |
Pages: |
5503-13 |
|
•
•
•
•
•
|
Publication |
First Author: |
Sekine H |
Year: |
2011 |
Journal: |
Mol Immunol |
Title: |
The dual role of complement in the progression of renal disease in NZB/W F(1) mice and alternative pathway inhibition. |
Volume: |
49 |
Issue: |
1-2 |
Pages: |
317-23 |
|
•
•
•
•
•
|
Publication |
First Author: |
Osanai T |
Year: |
2012 |
Journal: |
Diabetologia |
Title: |
Coupling factor 6-induced activation of ecto-F1F(o) complex induces insulin resistance, mild glucose intolerance and elevated blood pressure in mice. |
Volume: |
55 |
Issue: |
2 |
Pages: |
520-9 |
|
•
•
•
•
•
|
Publication |
First Author: |
Elvington M |
Year: |
2012 |
Journal: |
Blood |
Title: |
A targeted complement-dependent strategy to improve the outcome of mAb therapy, and characterization in a murine model of metastatic cancer. |
Volume: |
119 |
Issue: |
25 |
Pages: |
6043-51 |
|
•
•
•
•
•
|
Publication |
First Author: |
Harris JV |
Year: |
2012 |
Journal: |
Infect Immun |
Title: |
Sequential Plasmodium chabaudi and Plasmodium berghei infections provide a novel model of severe malarial anemia. |
Volume: |
80 |
Issue: |
9 |
Pages: |
2997-3007 |
|
•
•
•
•
•
|
Publication |
First Author: |
Lee E |
Year: |
2013 |
Journal: |
Proc Natl Acad Sci U S A |
Title: |
Inhibition of androgen receptor and β-catenin activity in prostate cancer. |
Volume: |
110 |
Issue: |
39 |
Pages: |
15710-5 |
|
•
•
•
•
•
|
Publication |
First Author: |
Wang Y |
Year: |
2016 |
Journal: |
Cancer Discov |
Title: |
Autocrine Complement Inhibits IL10-Dependent T-cell-Mediated Antitumor Immunity to Promote Tumor Progression. |
Volume: |
6 |
Issue: |
9 |
Pages: |
1022-35 |
|
•
•
•
•
•
|
Publication |
First Author: |
Wang F |
Year: |
2017 |
Journal: |
PLoS One |
Title: |
RhoA promotes epidermal stem cell proliferation via PKN1-cyclin D1 signaling. |
Volume: |
12 |
Issue: |
2 |
Pages: |
e0172613 |
|
•
•
•
•
•
|
Publication |
First Author: |
Lohman RJ |
Year: |
2017 |
Journal: |
Nat Commun |
Title: |
Exploiting a novel conformational switch to control innate immunity mediated by complement protein C3a. |
Volume: |
8 |
Issue: |
1 |
Pages: |
351 |
|
•
•
•
•
•
|
Publication |
First Author: |
Huang W |
Year: |
2018 |
Journal: |
J Immunol |
Title: |
A Novel Pkhd1 Mutation Interacts with the Nonobese Diabetic Genetic Background To Cause Autoimmune Cholangitis. |
Volume: |
200 |
Issue: |
1 |
Pages: |
147-162 |
|
•
•
•
•
•
|
Publication |
First Author: |
Huang L |
Year: |
2015 |
Journal: |
PLoS One |
Title: |
Severe Nephrotoxic Nephritis following Conditional and Kidney-Specific Knockdown of Stanniocalcin-1. |
Volume: |
10 |
Issue: |
9 |
Pages: |
e0138440 |
|
•
•
•
•
•
|
Publication |
First Author: |
Wang L |
Year: |
2018 |
Journal: |
FASEB J |
Title: |
GSK3-activated STAT5 regulates expression of SFRPs to modulate adipogenesis. |
Volume: |
32 |
Issue: |
9 |
Pages: |
4714-4726 |
|
•
•
•
•
•
|
Publication |
First Author: |
Lee J |
Year: |
2019 |
Journal: |
PLoS One |
Title: |
Irisin promotes C2C12 myoblast proliferation via ERK-dependent CCL7 upregulation. |
Volume: |
14 |
Issue: |
9 |
Pages: |
e0222559 |
|
•
•
•
•
•
|
Publication |
First Author: |
Kurihara RS |
Year: |
2005 |
Journal: |
Braz J Med Biol Res |
Title: |
Genetic potential for an acute inflammatory response in IgA glomerulonephritis in mice. |
Volume: |
38 |
Issue: |
12 |
Pages: |
1807-15 |
|
•
•
•
•
•
|
Publication |
First Author: |
Skopelja-Gardner S |
Year: |
2020 |
Journal: |
J Immunol |
Title: |
Complement Deficiencies Result in Surrogate Pathways of Complement Activation in Novel Polygenic Lupus-like Models of Kidney Injury. |
Volume: |
204 |
Issue: |
10 |
Pages: |
2627-2640 |
|
•
•
•
•
•
|
Publication |
First Author: |
Li Y |
Year: |
2019 |
Journal: |
Int Immunopharmacol |
Title: |
Interleukin-25 is upregulated in patients with systemic lupus erythematosus and ameliorates murine lupus by inhibiting inflammatory cytokine production. |
Volume: |
74 |
|
Pages: |
105680 |
|
•
•
•
•
•
|
Publication |
First Author: |
Scott-Hewitt N |
Year: |
2020 |
Journal: |
EMBO J |
Title: |
Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia. |
Volume: |
39 |
Issue: |
16 |
Pages: |
e105380 |
|
•
•
•
•
•
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Publication |
First Author: |
Hong J |
Year: |
2020 |
Journal: |
Int J Mol Sci |
Title: |
The Rho/Rac Guanine Nucleotide Exchange Factor Vav1 Regulates Hif-1α and Glut-1 Expression and Glucose Uptake in the Brain. |
Volume: |
21 |
Issue: |
4 |
|
|
•
•
•
•
•
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Publication |
First Author: |
Asega AF |
Year: |
2020 |
Journal: |
Sci Rep |
Title: |
Cleavage of proteoglycans, plasma proteins and the platelet-derived growth factor receptor in the hemorrhagic process induced by snake venom metalloproteinases. |
Volume: |
10 |
Issue: |
1 |
Pages: |
12912 |
|
•
•
•
•
•
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Publication |
First Author: |
Zarantonello A |
Year: |
2020 |
Journal: |
J Immunol |
Title: |
An Ultrahigh-Affinity Complement C4b-Specific Nanobody Inhibits In Vivo Assembly of the Classical Pathway Proconvertase. |
Volume: |
205 |
Issue: |
6 |
Pages: |
1678-1694 |
|
•
•
•
•
•
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Publication |
First Author: |
Jabri Y |
Year: |
2020 |
Journal: |
Int J Mol Sci |
Title: |
Cell-Type-Specific Complement Profiling in the ABCA4-/- Mouse Model of Stargardt Disease. |
Volume: |
21 |
Issue: |
22 |
|
|
•
•
•
•
•
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Publication |
First Author: |
Turgu B |
Year: |
2021 |
Journal: |
Oncogene |
Title: |
HACE1 blocks HIF1α accumulation under hypoxia in a RAC1 dependent manner. |
Volume: |
40 |
Issue: |
11 |
Pages: |
1988-2001 |
|
•
•
•
•
•
|
Publication |
First Author: |
Malik TH |
Year: |
2021 |
Journal: |
Proc Natl Acad Sci U S A |
Title: |
Gain-of-function factor H-related 5 protein impairs glomerular complement regulation resulting in kidney damage. |
Volume: |
118 |
Issue: |
13 |
|
|
•
•
•
•
•
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Publication |
First Author: |
Ding P |
Year: |
2020 |
Journal: |
Theranostics |
Title: |
C5aR1 is a master regulator in Colorectal Tumorigenesis via Immune modulation. |
Volume: |
10 |
Issue: |
19 |
Pages: |
8619-8632 |
|
•
•
•
•
•
|
Publication |
First Author: |
Tankersley CG |
Year: |
2001 |
Journal: |
J Appl Physiol (1985) |
Title: |
Selected contribution: variation in acute hypoxic ventilatory response is linked to mouse chromosome 9. |
Volume: |
90 |
Issue: |
4 |
Pages: |
1615-22; discussion 1606 |
|
•
•
•
•
•
|
Publication |
First Author: |
Chen MM |
Year: |
2021 |
Journal: |
Brain Behav Immun |
Title: |
Astrocytic Kir6.1 deletion aggravates neurodegeneration in the lipopolysaccharide-induced mouse model of Parkinson's disease via astrocyte-neuron cross talk through complement C3-C3R signaling. |
Volume: |
95 |
|
Pages: |
310-320 |
|
•
•
•
•
•
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Publication |
First Author: |
Gorelik A |
Year: |
2017 |
Journal: |
Front Cell Neurosci |
Title: |
Serping1/C1 Inhibitor Affects Cortical Development in a Cell Autonomous and Non-cell Autonomous Manner. |
Volume: |
11 |
|
Pages: |
169 |
|
•
•
•
•
•
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Publication |
First Author: |
Yi YS |
Year: |
2021 |
Journal: |
Front Immunol |
Title: |
Syk-MyD88 Axis Is a Critical Determinant of Inflammatory-Response in Activated Macrophages. |
Volume: |
12 |
|
Pages: |
767366 |
|
•
•
•
•
•
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Publication |
First Author: |
Yamanaka T |
Year: |
2016 |
Journal: |
Immunobiology |
Title: |
Release from Th1-type immune tolerance in spleen and enhanced production of IL-5 in Peyer's patch by cholera toxin B induce the glomerular deposition of IgA. |
Volume: |
221 |
Issue: |
4 |
Pages: |
577-85 |
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•
•
•
•
|
Publication |
First Author: |
Choi YJ |
Year: |
2022 |
Journal: |
Sci Rep |
Title: |
Promotion of the inflammatory response in mid colon of complement component 3 knockout mice. |
Volume: |
12 |
Issue: |
1 |
Pages: |
1700 |
|
•
•
•
•
•
|
Publication |
First Author: |
Gullstrand B |
Year: |
2009 |
Journal: |
Clin Exp Immunol |
Title: |
Complement classical pathway components are all important in clearance of apoptotic and secondary necrotic cells. |
Volume: |
156 |
Issue: |
2 |
Pages: |
303-11 |
|
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•
•
•
•
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Publication |
First Author: |
Block H |
Year: |
2016 |
Journal: |
Blood |
Title: |
Gnb isoforms control a signaling pathway comprising Rac1, Plcβ2, and Plcβ3 leading to LFA-1 activation and neutrophil arrest in vivo. |
Volume: |
127 |
Issue: |
3 |
Pages: |
314-24 |
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•
•
•
•
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Publication |
First Author: |
Peng W |
Year: |
2022 |
Journal: |
Front Aging Neurosci |
Title: |
Spatiotemporal patterns of gliosis and neuroinflammation in presenilin 1/2 conditional double knockout mice. |
Volume: |
14 |
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Pages: |
966153 |
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•
•
•
•
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Publication |
First Author: |
Shende R |
Year: |
2022 |
Journal: |
Front Immunol |
Title: |
Protective role of host complement system in Aspergillus fumigatus infection. |
Volume: |
13 |
|
Pages: |
978152 |
|
•
•
•
•
•
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Publication |
First Author: |
Chau DD |
Year: |
2022 |
Journal: |
FASEB J |
Title: |
Insulin stimulates atypical protein kinase C-mediated phosphorylation of the neuronal adaptor FE65 to potentiate neurite outgrowth by activating ARF6-Rac1 signaling. |
Volume: |
36 |
Issue: |
11 |
Pages: |
e22594 |
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•
•
•
•
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Publication |
First Author: |
Li H |
Year: |
2021 |
Journal: |
J Am Soc Nephrol |
Title: |
MicroRNA-23b-3p Deletion Induces an IgA Nephropathy-like Disease Associated with Dysregulated Mucosal IgA Synthesis. |
Volume: |
32 |
Issue: |
10 |
Pages: |
2561-2578 |
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•
•
•
•
•
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Publication |
First Author: |
Turgu B |
Year: |
2023 |
Journal: |
EMBO Rep |
Title: |
The HACE1 E3 ligase mediates RAC1-dependent control of mTOR signaling complexes. |
Volume: |
24 |
Issue: |
12 |
Pages: |
e56815 |
|
•
•
•
•
•
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Publication |
First Author: |
Wang J |
Year: |
2023 |
Journal: |
Sci Transl Med |
Title: |
Liver macrophages and sinusoidal endothelial cells execute vaccine-elicited capture of invasive bacteria. |
Volume: |
15 |
Issue: |
727 |
Pages: |
eade0054 |
|
•
•
•
•
•
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Publication |
First Author: |
Alajoleen RM |
Year: |
2024 |
Journal: |
Front Immunol |
Title: |
Tlr5 deficiency exacerbates lupus-like disease in the MRL/lpr mouse model. |
Volume: |
15 |
|
Pages: |
1359534 |
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•
•
•
•
•
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Publication |
First Author: |
Kelkka T |
Year: |
2014 |
Journal: |
Antioxid Redox Signal |
Title: |
Reactive oxygen species deficiency induces autoimmunity with type 1 interferon signature. |
Volume: |
21 |
Issue: |
16 |
Pages: |
2231-45 |
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•
•
•
•
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Publication |
First Author: |
Amorim A |
Year: |
1984 |
Journal: |
Cytogenet Cell Genet |
Title: |
Linkage studies on the ALADH polymorphism (Abstracts of meeting presentations: Human gene mapping 7, Los Angeles Conference (1983) Seventh International Workshop on Human Gene Mapping) |
Volume: |
37 (1-4) |
|
Pages: |
400 (Abstr.) (399-616) |
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•
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Protein |
Organism: |
Mus musculus/domesticus |
Length: |
81
 |
Fragment?: |
true |
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•
•
•
•
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Publication |
First Author: |
Thole V |
Year: |
1998 |
Journal: |
Virology |
Title: |
Rice tungro spherical virus polyprotein processing: identification of a virus-encoded protease and mutational analysis of putative cleavage sites. |
Volume: |
247 |
Issue: |
1 |
Pages: |
106-14 |
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•
•
•
•
•
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Publication |
First Author: |
Sekiguchi H |
Year: |
2005 |
Journal: |
Arch Virol |
Title: |
3C-like protease encoded by Rice tungro spherical virus is autocatalytically processed. |
Volume: |
150 |
Issue: |
3 |
Pages: |
595-601 |
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•
•
•
•
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Protein Domain |
Type: |
Domain |
Description: |
Viruses in the order Picornavirales infect different vertebrate, invertebrate, and plant hosts and are responsible for a variety of human, animal, and plant diseases. These viruses have a single-stranded, positive sense RNA genome that generally translates a large precursor polyprotein which is proteolytically cleaved after translation to generate mature functional viral proteins. This process is usually mediated by (more than one) proteases, and a 3C (for the family Picornaviridae) or 3C-like (3CL) protease (for other families) plays a central role in the cleavage of the viral precursor polyprotein. In addition to this key role, 3C/3C-like protease is able to cleave a number of host proteins to remodel the cellular environment for virus reproduction [, , , , , ]. The Picornavirales 3C/3C-like protease domain forms the MEROPS peptidase family C3 (picornain family) of clan PA.The 3C/3CL protease domain adopts a chymotrypsin-like fold with a cysteine nucleophile in place of a commonly found serine which suggests that the cysteine and serine perform an analogous catalytic function. The catalytic triad is made of a histidine, an aspartate/glutamate and the conserved cysteine in this sequential order. The 3C/3CL protease domain folds into two antiparallel beta barrels that are linked by a loop with a short α-helix in its middle, and flanked by two other α-helices at the N- and C-terminal. The two barrels are topologically equivalent and are formed by six antiparallel beta strands with the first four organised into a Greek key motif. The active-site residues are located in the cleft between the two barrels with the nucleophilic Cys from the C-terminal barrel and the general acid base His-Glu/Asp from the N-terminal barrel [, , ].This entry represents a rice tungro spherical waikavirus-type peptidase that belongs to MEROPS peptidase family C3G. It is a picornain 3C-type protease, and is responsible for the self-cleavage of the positive single-stranded polyproteins of a number of plant viral genomes. The location of the protease activity of the polyprotein is at the C-terminal end, adjacent and N-terminal to the putative RNA polymerase [, ]. |
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•
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Protein Domain |
Type: |
Family |
Description: |
Aspartate carbamoyltransferase (aspartate transcarbamylase, ATCase) is an allosteric enzyme that plays a central role in the regulation of the pyrimidine pathway in bacteria. The holoenzyme is a dodecamer composed of six catalytic chains, each with an active site, and six regulatory chains lacking catalytic activity []. The catalytic subunits exist as a dimer of catalytic trimers, (c3)2, while the regulatory subunits exist as a trimer of regulatory dimers, (r2)3, therefore the complete holoenzyme can be represented as (c3)2(r2)3. The association of the catalytic subunits c3 with the regulatory subunits r2 is responsible for the establishment of positive co-operativity between catalytic sites for the binding of aspartate and it dictates the pattern of allosteric response toward nucleotide effectors. ATCase from Escherichia coli is the most extensively studied allosteric enzyme []. The crystal structure of the T-state, the T-state with CTP bound, the R-state with N-phosphonacetyl-L-aspartate (PALA) bound, and the R-state with phosphonoacetamide plus malonate bound have been used in interpreting kinetic and mutational studies.A high-resolution structure of E. coli ATCase in the presence of PALA (a bisubstrate analog) allows a detailed description of the binding at the active site of the enzyme and allows a detailed model of the tetrahedral intermediate to be constructed. The entire regulatory chain has been traced showing that the N-terminal regions of the regulatory chains R1 and R6 are located in close proximity to each other and to the regulatory site. This portion of the molecule may be involved in the observed asymmetry between the regulatory binding sites as well as in the heterotropic response of the enzyme []. The C-terminal domain of the regulatory chains have a rubredoxin-like zinc-bound fold. ATCase from Enterobacter agglomerans (Erwinia herbicola) (Pantoea agglomerans) differs from the other investigated enterobacterial ATCases by its absence of homotropic co-operativity toward the substrate aspartate and its lack of response to ATP which is an allosteric effector (activator) of this family of enzymes. Nevertheless, the E. herbicola ATCase has the same quaternary structure, two trimers of catalytic chains with three dimers of regulatory chains, (c3)2(r2)3, as other enterobacterial ATCases and shows extensive primary structure conservation []. |
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•
•
•
•
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Protein Domain |
Type: |
Homologous_superfamily |
Description: |
Aspartate carbamoyltransferase (aspartate transcarbamylase, ATCase) is an allosteric enzyme that plays a central role in the regulation of the pyrimidine pathway in bacteria. The holoenzyme is a dodecamer composed of six catalytic chains, each with an active site, and six regulatory chains lacking catalytic activity []. The catalytic subunits exist as a dimer of catalytic trimers, (c3)2, while the regulatory subunits exist as a trimer of regulatory dimers, (r2)3, therefore the complete holoenzyme can be represented as (c3)2(r2)3. The association of the catalytic subunits c3 with the regulatory subunits r2 is responsible for the establishment of positive co-operativity between catalytic sites for the binding of aspartate and it dictates the pattern of allosteric response toward nucleotide effectors. ATCase from Escherichia coli is the most extensively studied allosteric enzyme []. The crystal structure of the T-state, the T-state with CTP bound, the R-state with N-phosphonacetyl-L-aspartate (PALA) bound, and the R-state with phosphonoacetamide plus malonate bound have been used in interpreting kinetic and mutational studies.A high-resolution structure of E. coli ATCase in the presence of PALA (a bisubstrate analog) allows a detailed description of the binding at the active site of the enzyme and allows a detailed model of the tetrahedral intermediate to be constructed. The entire regulatory chain has been traced showing that the N-terminal regions of the regulatory chains R1 and R6 are located in close proximity to each other and to the regulatory site. This portion of the molecule may be involved in the observed asymmetry between the regulatory binding sites as well as in the heterotropic response of the enzyme []. The C-terminal domain of the regulatory chains have a rubredoxin-like zinc-bound fold. ATCase from Enterobacter agglomerans (Erwinia herbicola) (Pantoea agglomerans) differs from the other investigated enterobacterial ATCases by its absence of homotropic co-operativity toward the substrate aspartate and its lack of response to ATP which is an allosteric effector (activator) of this family of enzymes. Nevertheless, the E. herbicola ATCase has the same quaternary structure, two trimers of catalytic chains with three dimers of regulatory chains, (c3)2(r2)3, as other enterobacterial ATCases and shows extensive primary structure conservation []. This entry represents the N-terminal domain superfamily. Structurally, this domain has a ferredoxin-like fold, which consists of an alpha+beta sandwich with antiparallel β-sheet. |
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•
•
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Protein Domain |
Type: |
Homologous_superfamily |
Description: |
Aspartate carbamoyltransferase (aspartate transcarbamylase, ATCase) is an allosteric enzyme that plays a central role in the regulation of the pyrimidine pathway in bacteria. The holoenzyme is a dodecamer composed of six catalytic chains, each with an active site, and six regulatory chains lacking catalytic activity []. The catalytic subunits exist as a dimer of catalytic trimers, (c3)2, while the regulatory subunits exist as a trimer of regulatory dimers, (r2)3, therefore the complete holoenzyme can be represented as (c3)2(r2)3. The association of the catalytic subunits c3 with the regulatory subunits r2 is responsible for the establishment of positive co-operativity between catalytic sites for the binding of aspartate and it dictates the pattern of allosteric response toward nucleotide effectors. ATCase from Escherichia coli is the most extensively studied allosteric enzyme []. The crystal structure of the T-state, the T-state with CTP bound, the R-state with N-phosphonacetyl-L-aspartate (PALA) bound, and the R-state with phosphonoacetamide plus malonate bound have been used in interpreting kinetic and mutational studies.A high-resolution structure of E. coli ATCase in the presence of PALA (a bisubstrate analog) allows a detailed description of the binding at the active site of the enzyme and allows a detailed model of the tetrahedral intermediate to be constructed. The entire regulatory chain has been traced showing that the N-terminal regions of the regulatory chains R1 and R6 are located in close proximity to each other and to the regulatory site. This portion of the molecule may be involved in the observed asymmetry between the regulatory binding sites as well as in the heterotropic response of the enzyme []. The C-terminal domain of the regulatory chains have a rubredoxin-like zinc-bound fold. ATCase from Enterobacter agglomerans (Erwinia herbicola) (Pantoea agglomerans) differs from the other investigated enterobacterial ATCases by its absence of homotropic co-operativity toward the substrate aspartate and its lack of response to ATP which is an allosteric effector (activator) of this family of enzymes. Nevertheless, the E. herbicola ATCase has the same quaternary structure, two trimers of catalytic chains with three dimers of regulatory chains, (c3)2(r2)3, as other enterobacterial ATCases and shows extensive primary structure conservation []. This entry represents the C-terminal domain superfamily. |
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Protein Domain |
Type: |
Domain |
Description: |
Aspartate carbamoyltransferase (aspartate transcarbamylase, ATCase) is an allosteric enzyme that plays a central role in the regulation of the pyrimidine pathway in bacteria. The holoenzyme is a dodecamer composed of six catalytic chains, each with an active site, and six regulatory chains lacking catalytic activity []. The catalytic subunits exist as a dimer of catalytic trimers, (c3)2, while the regulatory subunits exist as a trimer of regulatory dimers, (r2)3, therefore the complete holoenzyme can be represented as (c3)2(r2)3. The association of the catalytic subunits c3 with the regulatory subunits r2 is responsible for the establishment of positive co-operativity between catalytic sites for the binding of aspartate and it dictates the pattern of allosteric response toward nucleotide effectors. ATCase from Escherichia coli is the most extensively studied allosteric enzyme []. The crystal structure of the T-state, the T-state with CTP bound, the R-state with N-phosphonacetyl-L-aspartate (PALA) bound, and the R-state with phosphonoacetamide plus malonate bound have been used in interpreting kinetic and mutational studies.A high-resolution structure of E. coli ATCase in the presence of PALA (a bisubstrate analog) allows a detailed description of the binding at the active site of the enzyme and allows a detailed model of the tetrahedral intermediate to be constructed. The entire regulatory chain has been traced showing that the N-terminal regions of the regulatory chains R1 and R6 are located in close proximity to each other and to the regulatory site. This portion of the molecule may be involved in the observed asymmetry between the regulatory binding sites as well as in the heterotropic response of the enzyme []. The C-terminal domain of the regulatory chains have a rubredoxin-like zinc-bound fold. ATCase from Enterobacter agglomerans (Erwinia herbicola) (Pantoea agglomerans) differs from the other investigated enterobacterial ATCases by its absence of homotropic co-operativity toward the substrate aspartate and its lack of response to ATP which is an allosteric effector (activator) of this family of enzymes. Nevertheless, the E. herbicola ATCase has the same quaternary structure, two trimers of catalytic chains with three dimers of regulatory chains, (c3)2(r2)3, as other enterobacterial ATCases and shows extensive primary structure conservation []. This entry represents the C-terminal domain. |
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Protein Domain |
Type: |
Domain |
Description: |
Aspartate carbamoyltransferase (aspartate transcarbamylase, ATCase) is an allosteric enzyme that plays a central role in the regulation of the pyrimidine pathway in bacteria. The holoenzyme is a dodecamer composed of six catalytic chains, each with an active site, and six regulatory chains lacking catalytic activity []. The catalytic subunits exist as a dimer of catalytic trimers, (c3)2, while the regulatory subunits exist as a trimer of regulatory dimers, (r2)3, therefore the complete holoenzyme can be represented as (c3)2(r2)3. The association of the catalytic subunits c3 with the regulatory subunits r2 is responsible for the establishment of positive co-operativity between catalytic sites for the binding of aspartate and it dictates the pattern of allosteric response toward nucleotide effectors. ATCase from Escherichia coli is the most extensively studied allosteric enzyme []. The crystal structure of the T-state, the T-state with CTP bound, the R-state with N-phosphonacetyl-L-aspartate (PALA) bound, and the R-state with phosphonoacetamide plus malonate bound have been used in interpreting kinetic and mutational studies.A high-resolution structure of E. coli ATCase in the presence of PALA (a bisubstrate analog) allows a detailed description of the binding at the active site of the enzyme and allows a detailed model of the tetrahedral intermediate to be constructed. The entire regulatory chain has been traced showing that the N-terminal regions of the regulatory chains R1 and R6 are located in close proximity to each other and to the regulatory site. This portion of the molecule may be involved in the observed asymmetry between the regulatory binding sites as well as in the heterotropic response of the enzyme []. The C-terminal domain of the regulatory chains have a rubredoxin-like zinc-bound fold. ATCase from Enterobacter agglomerans (Erwinia herbicola) (Pantoea agglomerans) differs from the other investigated enterobacterial ATCases by its absence of homotropic co-operativity toward the substrate aspartate and its lack of response to ATP which is an allosteric effector (activator) of this family of enzymes. Nevertheless, the E. herbicola ATCase has the same quaternary structure, two trimers of catalytic chains with three dimers of regulatory chains, (c3)2(r2)3, as other enterobacterial ATCases and shows extensive primary structure conservation []. |
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Protein Domain |
Type: |
Family |
Description: |
Hydrogenases catalyse the reversible oxidation of molecular hydrogen and play a vital role in anaerobic metabolism. Metal-containing hydrogenases are subdivided into three classes: Fe ('iron only') hydrogenases; Ni-Fe hydrogenases; and Ni-Fe-Se hydrogenases []. Hydrogen oxidation is coupled to the reduction of electron acceptors (such as oxygen, nitrate, sulphate, carbon dioxide and fumarate), whereas proton reduction (hydrogen evolution) is essential in pyruvate fermentation or in the disposal of excess electrons.The Ni-Fe hydrogenases,when isolated, are found to catalyse both hydrogen evolution and uptake, with low-potential multihaem cytochromes, such as cytochrome c3, acting as either electron donors or acceptors, depending on their oxidation state. Both periplasmic (soluble) and membrane-bound hydrogenases are known.The Ni-Fe hydrogenases are heterodimeric proteins consisting of small (S) and large (L) subunits. The small subunit contains three iron-sulphur clusters (two [4Fe-4S]and one [3Fe-4S]); the large subunit contains a nickel ion []. Small subunits of membrane-bound Ni-Fe hydrogenases contain a C-terminal domain of about 40 residues that is absent in periplasmic forms.The 3D structure of the Ni-Fe hydrogenase from Desulfovibrio gigas has been determined at 2.85A resolution []. The small subunit consists of two domains, I(S) and II(S). The alpha/beta twisted open sheet structure of the N-terminal I(S) domain is similar to that of flavodoxin; the C-terminal II(S) domain contains two α-helices and has no β-structure. The Fe-S clusters are distributed almost along a straight line, with the [3Fe-4S]cluster located half-way between the two [4Fe-4S]clusters. The two [4Fe-4S]clusters have been termed proximal (prox) and distal (dist), based on their distance to the Ni atom. Domain I(S) binds the [4Fe-4S]prox cluster, while domain II(S) binds the [4Fe-4S]dist and [3Fe-4S]clusters. The [4Fe-4S]prox cluster is coordinated by Cys-17, Cys-20, Cys-112 and Cys-148; [4Fe-4S]dist is coordinated by His-185, Cys-188, Cys-213 and Cys-219; and [3Fe-4S]is coordinated by Cys-228, Cys-246 and Cys-249 [4Fe-4S]dist is the first known example of a [4Fe-4S]cluster in protein structure ligated by a His side chain. A crown of acidic residues surrounds the partially-exposed His-185 and this might provide a recognition site for the redox partner (cytochrome c3) []. A mechanism of electron transfer from the Ni active site through the Fe-S clusters to the cytochrome c3 has been suggested []. The role of the [3Fe-4S]cluster is not clear: its high redox potential and its absence from some homologous hydrogenases put its involvement in electron transfer in doubt []. |
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