Molecular Cloning and Identification of  -Acyl-D-glucosamine 2-Epimerase from Porcine Kidney as a Renin-binding Protein

Maru, Isafumi; Ohta, Yasuhiro; Murata, Kousaku; Tsukada, Yoji

doi:10.1074/jbc.271.27.16294

Cited by 119 publications

(57 citation statements)

References 27 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In order to determine the length of incubation that would result in optimal conversion of radiolabeled substrates, a time course was performed using compound 9c ( Figure 6B). This experiment indicated that, at least for Ac 4 ManNAc, conversion of exogenous peracetylated substrate to cytosolic intermediates was optimal between 20 and 24 hours.…”

Section: Analysis Of Cytosolic Mannosamine Metabolites Using 14 C-ac mentioning

confidence: 95%

Substrate Specificity of the Sialic Acid Biosynthetic Pathway

et al. 2001

View full text Add to dashboard Cite

Unnatural analogues of sialic acid can be delivered to mammalian cell surfaces through the metabolic transformation of unnatural N-acetylmannosamine (ManNAc) derivatives. In previous studies, mannosamine analogues bearing simple N-acyl groups up to five carbon atoms in length were recognized as substrates by the biosynthetic machinery and transformed into cell surface sialoglycoconjugates [Keppler, O. T., et al. (2001) Glycobiology 11, 11R-18R]. Such structural alterations to cell surface glycans can be used to probe carbohydrate-dependent phenomena. This report describes our investigation into the extent of tolerance of the pathway toward additional structural alterations of the N-acyl substituent of ManNAc. A panel of analogues with ketone-containing N-acyl groups that varied in the length or steric bulk was chemically synthesized and tested for metabolic conversion to cell surface glycans. We found that extension of the N-acyl chain to six, seven, or eight carbon atoms dramatically reduced utilization by the biosynthetic machinery. Likewise, branching from the linear chain reduced metabolic conversion. Quantitation of metabolic intermediates suggested that cellular metabolism is limited by the phosphorylation of the N-acylmannosamines by ManNAc 6-kinase in the first step of the pathway. This was confirmed by enzymatic assay of the partially purified enzyme with unnatural substrates. Identification of ManNAc 6-kinase as a bottleneck for unnatural sialic acid biosynthesis provides a target for expanding the metabolic promiscuity of mammalian cells.

show abstract

Section: Analysis Of Cytosolic Mannosamine Metabolites Using 14 C-ac mentioning

confidence: 95%

Substrate Specificity of the Sialic Acid Biosynthetic Pathway

et al. 2001

View full text Add to dashboard Cite

show abstract

“…We and others found that a prorenin binding protein exists on the surface of plasma membrane in humans (1)(2)(3)(4)(5) and in rat tissues (6) and that its binding to prorenin activates proenzyme by a conformational change without proteolytically cleaving the 43-amino acid prosegment off the main body of active (mature) renin. Because the prorenin receptor localizes to the kidney (4), the locally activated prorenin by prorenin receptor can generate angiotensin I (AngI) and II (AngII) locally and exert its local action, leading to renal damage.…”

mentioning

confidence: 99%

Contribution of Nonproteolytically Activated Prorenin in Glomeruli to Hypertensive Renal Damage

Ichihara¹,

Kaneshiro²,

Takemitsu³

et al. 2006

Journal of the American Society of Nephrology

132

128

View full text Add to dashboard Cite

Prorenin is activated without proteolysis by binding of prorenin receptor to the pentameric "handle region" (HR) of prorenin prosegment. It was hypothesized that such activation occurs in the kidneys of hypertensive rats and causes tissue reninangiotensin system (RAS) activation and end-organ damage. Because the HR's binding to its binding protein made the adjacent tetrameric "gate region" (GR) accessible to its specific antibody, immunohistochemistry of the GR was performed to test the hypothesis. Methods also were devised specifically to inhibit the nonproteolytic activation by the decapeptide corresponding to the HR as a decoy. Immunohistochemistry of the GR demonstrated that the majority of nonproteolytically activated prorenin is present in podocytes of the kidneys from stroke-prone spontaneously hypertensive rats, in which activation of renal tissue RAS, proteinuria, and glomerulosclerosis occurred. Continuous subcutaneous administration of the HR decoy peptide completely inhibited both nonproteolytic activation of tissue prorenin and activation of tissue RAS without affecting circulating RAS or arterial pressure and significantly attenuated the development and progression of proteinuria and glomerulosclerosis. These studies clearly demonstrated that nonproteolytic activation of prorenin in glomeruli is critically involved in renal tissue RAS activation, leading to renal damage in hypertensive animals.

show abstract

“…53) As for the = -barrel, we have confirmed that a porcine kidney bifunctional protein, renin-binding protein [N-acyl-D-glucosamine 2-epimerase (AGE)], 54,55) a novel glycosaminoglycan-degrading enzyme of unsaturated glucuronyl hydrolase (UGL) of Bacillus sp. GL1, 56,57) a plant cell wall-degrading enzyme (B. subtilis unsaturated galacturonyl hydrolase) YteR, 58) and an AGE structural homolog, YihS, (unpublished) of S. typhimurium have = -barrel structures as a basic scaffold.…”

Section: Structural Features Of Polysaccharide Lyasementioning

confidence: 65%