Protein Variants | Comment | Organism |
---|---|---|
additional information | construction of conditional deficiency of the glycocalyx-modifying enzyme N-deacetylase-N-sulfotransferase-1 (Ndst1f/f TekCre+) which reduces aortic allograft inflammation. Conditional donor allograft Ndst1 deficiency (Ndst1-/-, C57Bl/6 background) is compared to systemic treatment with M-T7, a broad-spectrum chemokine glycosaminoglycan (GAG) inhibitor. Early rejection is significantly reduced in Ndst1-/- kidneys engrafted into wild-type BALB/c mice (Ndst1+/+) and comparable to M-T7 treatment in C57Bl/6 allografts. M-T7 is a 37 kDa Myxomavirus-derived secreted glycoprotein that possesses both broad spectrum, species-independent, C, CC and CXC chemokine inhibitory activity and a rabbit species-specific interferon gamma (IFNgamma) inhibitory activity. M-T7 activity is blunted in Ndst1-deficient mouse donor aortic transplants, a model for chronic TAV and vascular injury, but not in CC chemokine receptor deficient aortic allograft transplants, supporting M-T7 interference with chemokine-GAG interactions. M-T7 loses activity in Ndst1-/- allografts, while M-T7 point mutants with modified GAG chemokine binding display a range of anti-rejection activity. CD3+ T cells, HS and CXC chemokine staining, gene expression in NFkappaB and JAK/STAT pathways, and HS and CS disaccharide content are significantly altered with reduced rejection | Mus musculus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
extracellular | - |
Mus musculus | - |
- |
glycocalyx | - |
Mus musculus | 30112 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine | Mus musculus | - |
adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine | - |
? | |
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine | Mus musculus C57BL/6 | - |
adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mus musculus | Q3UHN9 | - |
- |
Mus musculus C57BL/6 | Q3UHN9 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
aorta | - |
Mus musculus | - |
endothelial cell | - |
Mus musculus | - |
myeloid progenitor cell | - |
Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine | - |
Mus musculus | adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine | - |
? | |
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine | - |
Mus musculus C57BL/6 | adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine | - |
? |
Synonyms | Comment | Organism |
---|---|---|
glycocalyx-modifying enzyme | - |
Mus musculus |
N-deacetylase-N-sulfotransferase-1 | - |
Mus musculus |
Ndst1 | - |
Mus musculus |
General Information | Comment | Organism |
---|---|---|
malfunction | selective deletion of heparan sulfotransferase enzyme, Ndst1, in donor endothelial and myeloid precursor cells significantly decreases acute allograft rejection, overview. Ndst1 deficiency in donor renal allografts significantly reduces histopathological markers for early renal allograft rejection. M-T7 (Myxomavirus-derived secreted glycoprotein that possesses a broad spectrum, species-independent, C, CC and CXC chemokine inhibitory activity) treatment significantly reduces histopathological markers for renal allograft rejection. M-T7 and M-T7 point mutant treatment have variable efficacy in WT and Ndst1-/- allografts. Reduced HS and chemokine immunoreactivity is associated with reduced rejection | Mus musculus |
physiological function | N-deacetylase-N-sulfotransferase-1 (Ndst1) acts as a central modifying enzyme in heparan sulfate (HS), catalyzing sulfate conjugation to carbohydrates. Modification of HS and chemokine interactions in whole-organ renal allografts, overview | Mus musculus |