4.6.1.18	evolution	the enzyme belongs to the pancreatic-type secretory ribonuclease superfamily	729310	
4.6.1.18	evolution	the enzyme belongs to the pancreatic-type secretory ribonuclease superfamily as a unique natively dimeric member	729310	
4.6.1.18	evolution	the enzyme belongs to the vertebrate pancreatic-like RNase A superfamily, sequence comparisons and phylogenetic analysis, overview	729713	
4.6.1.18	evolution	the enzyme is a member of the pancreatic ribonuclease (RNase) superfamily	730422	
4.6.1.18	evolution	the enzyme is one of the key models in studies of evolutionary innovation and functional diversification, evolution and the function of Caniformia RNASE1 genes, phylogenetic analysis, overview. Four independent gene duplication events in the families of superfamily Musteloidea, including Procyonidae, Ailuridae, Mephitidae and Mustelidae	730952	
4.6.1.18	malfunction	mechanistic model for the denaturation of bovine pancreatic ribonuclease A in urea, a direct interaction between urea and protonated histidine as the initial step for protein inactivation followed by hydrogen bond formation with polar residues, and the breaking of hydrophobic collapse as the final steps for protein denaturation	707508	
4.6.1.18	malfunction	RNase A tandem enzymes, in which two RNase A molecules are artificially connected by a peptide linker, and thus have a pseudodimeric structure, exhibit remarkable cytotoxic activity, but can be inhibited by the cytosolic ribonuclease inhibitor in vitro. Structure modeling, overview	717596	
4.6.1.18	metabolism	the enzyme lacks cytotoxic activity as it is inactivated by intracellular cytosolic ribonuclease inhibitor	750772	
4.6.1.18	additional information	analysis of synthesis and maturation, folding, quality control, and secretion, of pancreatic RNase in the endoplasmic reticulum of live cells, overview. Human RNase folds rapidly and is secreted mainly in glycosylated forms	717861	
4.6.1.18	additional information	analysis of synthesis and maturation, folding, quality control, and secretion, of pancreatic RNase in the endoplasmic reticulum of live cells, overview. In contrast to the slow in vitro refolding, the protein folds almost instantly after translation and translocation into the endoplasmatic reticulum lumen. Despite high stability of the native protein, only about half of the RNase reaches a secretion competent, monomeric form and is rapidly transported from the rough endoplasmic reticulum via the Golgi complex to the extracellular space	717861	
4.6.1.18	additional information	analysis of the disulfide bond formation phase in detail in the oxidative folding, as the first of two folding phases, of RNase A, overview. Comparision of folding intermediates of reduced RNase A obtained at 25°C and different pH values from pH 4.0, pH 7.0, to pH 10.0, shuffling and transformation of different intermediate types, overview. The preconformational folding phase coupled with disulfide bond formation can be divided into two distinct subphases, a kinetic (or stochastic) disulfide bond formation phase and a thermodynamic disulfide bond reshuffling phase. The transition from kinetically formed to thermodynamically stabilized disulfide bond intermediates are induced by hydrophobic nucleation as well as generation of the native interactions	717242	
4.6.1.18	additional information	arginine 39 is crucial for the dsRNA melting activity, and Gly38 is required, both these residues are not directly involved in the RNA cleavage activity	718274	
4.6.1.18	additional information	domain swapping, the process in which a structural unit is exchanged between monomers to create a dimer containing two versions of the monomeric fold, is believed to be an important mechanism for oligomerization and the formation of amyloid fibrils. In RNase residue P114 acts as a conformational gatekeeper, regulating interconversion between monomer and domain-swapped dimer forms, with cis and trans conformation, isomerization at P114 may facilitate population of a partially unfolded intermediate or alternative structure competent for domain swapping, overview	717990	
4.6.1.18	additional information	pancreatic ribonuclease A shows domain swapping, a type of oligomerization in which monomeric proteins exchange a structural element, resulting in oligomers whose subunits recapitulate the native, monomeric fold, under extreme conditions, such as lyophilization from acetic acid. The major domain swaps dimer form of RNase A exchanges a beta-strand at its C-terminus to form a C-terminal domain-swapped dimer, mechanism, overview. Domain swapping occurs via a local high-energy fluctuation at the C-terminus	718368	
4.6.1.18	additional information	RNA subsites and reaction mechanism catalyzed by RNase A, molecular interactions between the RNA substrate and residues of the catalytic groove. The following residues are known to interact with each subsite: Lys66 (P0), Thr45 and Asp83 (B1), Gln11, His12, Lys41, His119, and Asp121 (P1), Asn71 and Glu111 (B2), and Lys7 and Arg10 (P2). Structure-function relationship, overview	729713	
4.6.1.18	additional information	RNA subsites and reaction mechanism catalyzed by RNase A, molecular interactions between the RNA substrate and residues of the catalytic groove. The following residues are known to interact with each subsite: Lys66 (P0), Thr45 and Asp83 (B1), Gln11, His12, Lys41, His119, and Asp121 (P1), Asn71 and Glu111 (B2), and Lys7 and Arg10 (P2). Structure-function relationship, overview. Potential role for catalytic base His119 in ligand discrimination and/or stabilization in addition to its critical role in catalysis, molecular dynamic simulations show that His119 adopts both rotameric positions in solution, most likely experiencing conformational exchange over the course of a catalytic reaction. Functional importance of long-range conformational rearrangements in RNase A	729713	
4.6.1.18	additional information	the enzyme performs 3D domain swapping, a process by which two or more protein molecules exchange part of their structure to form intertwined dimers or higher oligomers	729327	
4.6.1.18	additional information	very subtle structural, chemical, and potentially motional variations contribute to ligand discrimination in the enzyme	718374	
4.6.1.18	physiological function	cytotoxic human pancreatic ribonuclease variant PE5 is able to cleave nuclear RNA, inducing the apoptosis of cancer cells and reducing the amount of P-glycoprotein in different multidrug-resistant cell lines	730422	
4.6.1.18	physiological function	His12 acts mainly as a general base in the catalytic process of RNase A	706955	
4.6.1.18	physiological function	pancreatic ribonuclease is a digestive enzyme	730952	
4.6.1.18	physiological function	the enzyme has almost no anti-tumoral property in pancreatic adenocarcinoma cell lines and in nontumorigenic cells as normal control, and is largely ineffective as anti-proliferative and pro-apoptotic agent	729310	
4.6.1.18	physiological function	the enzyme has good anti-tumoral property in pancreatic adenocarcinoma cell lines and in nontumorigenic cells as normal control, it stimulates a strong anti-proliferative and pro-apoptotic effect in cancer cells. The enzyme triggers Beclin1-mediated autophagic cancer cell death, providing evidence that high proliferation rate of cancer cells may render them more susceptible to autophagy by treatment with the enzyme	729310	
4.6.1.18	physiological function	the human isozymes have evolved additional biological activities, often linked to innate host defense, neurotoxicity, angiogenesis, and immunosuppressive and/or antibacterial/antiviral activities	729713