Biomaterial Database

5'-Diphosphoadenosine 3'-phosphate is a potent inhibitor of bovine pancreatic ribonuclease A. 1997

N Russo, and R Shapiro, and B L Vallee

Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.

As a first step toward the development of stable, selective, and potent inhibitors of those members of the pancreatic RNase superfamily that induce biological responses, we have focussed on low molecular weight compounds and studied their interactions with the active-site of bovine pancreatic ribonuclease A (RNase A). A new inhibitor is described, 5'-diphosphoadenosine 3'-phosphate, which binds to RNase A more tightly than any previous low molecular weight compound: its Ki value of 1.3 microM at pH 7 is 8-fold lower than that for uridine-vanadate, a transition-state analog, and 110-fold lower than that for 2'-CMP, one of the best-characterized RNase A ligands. The new inhibitor is found to contact RNase A residues that are conserved in several homologous mammalian RNases and hence should be able to serve as a basis for the design of even tighter-binding inhibitors of these enzymes.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D010179	Pancreas	A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D003568	Cytidine Monophosphate	Cytidine (dihydrogen phosphate). A cytosine nucleotide containing one phosphate group esterified to the sugar moiety in the 2', 3' or 5' position.	CMP,Cytidylic Acid,2'-CMP,3'-CMP,Cytidylic Acids,2' CMP,3' CMP,Acid, Cytidylic,Acids, Cytidylic,Monophosphate, Cytidine
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D000227	Adenine Nucleotides		Adenine Nucleotide,Adenosine Phosphate,Adenosine Phosphates,Nucleotide, Adenine,Nucleotides, Adenine,Phosphate, Adenosine,Phosphates, Adenosine
D000244	Adenosine Diphosphate	Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.	ADP,Adenosine Pyrophosphate,Magnesium ADP,MgADP,Adenosine 5'-Pyrophosphate,5'-Pyrophosphate, Adenosine,ADP, Magnesium,Adenosine 5' Pyrophosphate,Diphosphate, Adenosine,Pyrophosphate, Adenosine
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D012259	Ribonuclease, Pancreatic	An enzyme that catalyzes the endonucleolytic cleavage of pancreatic ribonucleic acids to 3'-phosphomono- and oligonucleotides ending in cytidylic or uridylic acids with 2',3'-cyclic phosphate intermediates. EC 3.1.27.5.	RNase A,Ribonuclease A,Pancreatic RNase,RNase I,Ribonuclease (Pancreatic),Ribonuclease I,Pancreatic Ribonuclease,RNase, Pancreatic