Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two mutants of the cysteine proteinase inhibitor, stefin B, were prepared by ligating the amino-terminal region from cystatin C and kininogen, members of two other families of cystatin superfamily. The mutant proteins were expressed in Escherichia coli and purified to homogeneity. Inhibition and kinetic constants were determined for authentic and mutated stefins against the four different cysteine proteinases, papain and human cathepsins B, L and H. Inhibition of both amino-terminal elongated stefin B mutants was decreased particularly for cathepsin H. A model of the tertiary structure of cathepsin H and its complex with stefin B was constructed. The framework for the model of cathepsin H consisted of structurally conserved regions from tertiary structures of three cysteine proteinases. Variable regions were selected from fragments of other proteins from the protein data base. We suggest that reduced binding of stefins with elongated amino termini is caused by the mini chain of cathepsin H which is probably in close proximity to the amino termini in the complexes. This mini chain is bridged to Cys214 and has already been proposed to be responsible for the aminopeptidase activity of cathepsin H. We conclude that the amino-terminal region of stefin B plays an important role in determining the strength of inhibition of cathepsin H.
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PMID:Elongation on the amino-terminal part of stefin B decreases inhibition of cathepsin H. 792 5

Highly purified human brain cathepsin H (EC 3.4.22.16) was used to study its involvement in degradation of different brain peptides. Its action was determined to be selective. On Leu-enkephalin, dynorphin (1-6), dynorphin (1-13), alpha-neoendorphin, and Lys-bradykinin, it showed a preferential aminopeptidase activity by cleaving off hydrophobic or basic amino acids. It showed no aminopeptidase activity on bradykinin, which has Pro adjacent to its N-terminal amino acid, on neurotensin with blocked N-terminal amino acid, or on dermorphin with second amino acid D-alanine. After prolonged incubation, cathepsin H acted as an endopeptidase. Dermorphin and dynorphin (1-13) were cleaved at bonds with Phe in the P2 position, while dynorphin (1-6), alpha-neoendorphin, bradykinin and Lys-bradykinin were cleaved at bonds with Gly in the P2 position. Further on, it was shown that human brain cathepsin H activity could be controlled in vivo by cystatin C in its full-length form or its [delta1-10] variant, already known to be co-localized in astrocytes, since the Ki values for the inhibition are in the 10(-10) M range.
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PMID:Human brain cathepsin H as a neuropeptide and bradykinin metabolizing enzyme. 1512 51

Acute renal failure (ARF) is a frequent problem in the intensive care unit and is associated with a high mortality. Early recognition could help clinical management, but current indices lack sufficient predictive value for ARF. Therefore, there might be a need for biomarkers in detecting renal tubular injury and/or dysfunction at an early stage before a decline in glomerular filtration rate is noted by an increased serum creatinine. A MEDLINE/PubMed search was performed, including all articles about biomarkers for ARF. All publication types, human and animal studies, or subsets were searched in English language. An extraction of relevant articles was made for the purpose of this narrative review. These biomarkers include tubular enzymes (alpha- and pi-glutathione S-transferase, N-acetyl-glucosaminidase, alkaline phosphatase, gamma-glutamyl transpeptidase, Ala-(Leu-Gly)-aminopeptidase, and fructose-1,6-biphosphatase), low-molecular weight urinary proteins (alpha1- and beta2-microglobulin, retinol-binding protein, adenosine deaminase-binding protein, and cystatin C), Na+/H+ exchanger, neutrophil gelatinase-associated lipocalin, cysteine-rich protein 61, kidney injury molecule 1, urinary interleukins/adhesion molecules, and markers of glomerular filtration such as proatrial natriuretic peptide (1-98) and cystatin C. These biomarkers, detected in urine or serum shortly after tubular injury, have been suggested to contribute to prediction of ARF and need for renal replacement therapy. However, excretion of these biomarkers may also increase after reversible and mild dysfunction and may not necessarily be associated with persistent or irreversible damage. Large prospective studies in human are needed to demonstrate an improved outcome of biomarker-driven management of the patient at risk for ARF.
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PMID:Biomarkers of acute renal injury and renal failure. 1691 49