Biomaterial Database

The molecular structure of the complex of Ascaris chymotrypsin/elastase inhibitor with porcine elastase. 1994

K Huang, and N C Strynadka, and V D Bernard, and R J Peanasky, and M N James

Department of Biochemistry, University of Alberta, Edmonton, Canada.

BACKGROUND The intestinal parasitic worm, Ascaris suum, produces a variety of protein inhibitors that defend the organism against the host's proteinases. Eight different proteins from Ascaris suum have been identified as inhibitors of serine proteinases, targeting chymotrypsin, elastase and trypsin. These inhibitors share 30-40% sequence identity with one another, but have virtually no sequence identity with members of any of the other families of serine proteinase inhibitors. RESULTS The crystal structure of the complex of porcine pancreatic elastase with a chymotrypsin/elastase inhibitor from Ascaris suum (the C/E-1 inhibitor) has been solved to 2.4 A resolution by the molecular replacement method. The C/E-1 inhibitor exhibits a novel folding motif. There are only two small beta-sheets and two single-turn 3(10)-helices in this inhibitor. Unlike the majority of proteins, the C/E-1 inhibitor does not have a hydrophobic core. The presence and unique topography of the five disulfide bridges suggests that they play important roles in maintaining the tertiary structure of the inhibitor. In addition, the side chains of several charged residues from electrostatic and hydrogen-bonding cascades, which also probably compensate for the lack of extensive secondary structures and a hydrophobic core. The reactive-site loop of this inhibitor displays a conformation that is characteristic of most serine proteinase inhibitors. CONCLUSIONS The structure of the C/E-1 inhibitor confirms that inhibitors from Ascaris suum belong to a novel family of proteinase inhibitors. It also provides conclusive evidence for the correct disulfide bridge connections. The C/E-1 inhibitor probably acts by a common inhibitory mechanism proposed for other substrate-like protein inhibitors of serine proteinases. The unusual molecular scaffolding presents a challenge to current folding algorithms. Proteins like the C/E-1 inhibitor may provide a valuable model system to study how the primary sequence of a protein dictates its three-dimensional structure.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
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.
D010196	Pancreatic Elastase	A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25,000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. EC 3.4.21.36.	Elastase,Pancreatopeptidase,Elastase I,Pancreatic Elastase I,Elastase I, Pancreatic,Elastase, Pancreatic
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D002918	Chymotrypsin	A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.	Alpha-Chymotrypsin Choay,Alphacutanée,Avazyme
D006860	Hydrogen Bonding	A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.	Hydrogen Bonds,Bond, Hydrogen,Hydrogen Bond
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
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