Structure of the complex of bovine pancreatic phospholipase A2 with a transition-state analogue. 1998

K Sekar, and A Kumar, and X Liu, and M D Tsai, and M H Gelb, and M Sundaralingam
Biological Macromolecular Structure Center, Departments of Chemistry and Biochemistry, 100 West 18th Avenue, The Ohio State University, Columbus, OH 43210-1185, USA.

The 1.89 A resolution structure of the complex of bovine pancreatic phospholipase A2 (PLA2) with the transition-state analogue L-1-O-octyl-2-heptylphosphonyl-sn-glycero-3-phosphoethanolamine (TSA) has been determined. The crystal of the complex is trigonal, space group P3121, a = b = 46.58 and c = 102.91 A and isomorphous to the native recombinant wild type (WT). The structure was refined to a final crystallographic R value of 18.0% including 957 protein atoms, 88 water molecules, one calcium ion and all 31 non-H atoms of the inhibitor at 1.89 A resolution. In all, 7 726 reflections [F>2sigma(F)] were used between 8.0 and 1.89 A resolution. The inhibitor is deeply locked into the active-site cleft and coordinates to the calcium ion by displacing the two water molecules in the calcium pentagonal bipyramid by the anionic O atoms of the phosphate and phosphonate group. The hydroxyl group of Tyr69 hydrogen bonds to the second anionic O atom of the phosphate group while that of the phosphonate group replaces the third water, 'catalytic' water, which forms a hydrogen bond to Ndelta1 of His48. The fourth water which also shares Ndelta1 of His48 is displaced by the steric hinderance of the inhibitor. The fifth conserved structural water is still present in the active site and forms a network of hydrogen bonds with the surrounding residues. The structure is compared to the other known TSA-PLA2 complexes.

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.
D010741 Phospholipases A Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.
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
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
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D054467 Phospholipases A2 Phospholipases that hydrolyze the acyl group attached to the 2-position of PHOSPHOGLYCERIDES. Lecithinase A2,Phospholipase A2
D018360 Crystallography, X-Ray The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) X-Ray Crystallography,Crystallography, X Ray,Crystallography, Xray,X Ray Crystallography,Xray Crystallography,Crystallographies, X Ray,X Ray Crystallographies

Related Publications

K Sekar, and A Kumar, and X Liu, and M D Tsai, and M H Gelb, and M Sundaralingam
December 1990, Science (New York, N.Y.),
K Sekar, and A Kumar, and X Liu, and M D Tsai, and M H Gelb, and M Sundaralingam
December 1990, Science (New York, N.Y.),
K Sekar, and A Kumar, and X Liu, and M D Tsai, and M H Gelb, and M Sundaralingam
January 1978, European journal of biochemistry,
K Sekar, and A Kumar, and X Liu, and M D Tsai, and M H Gelb, and M Sundaralingam
July 1983, Journal of molecular biology,
K Sekar, and A Kumar, and X Liu, and M D Tsai, and M H Gelb, and M Sundaralingam
March 1981, Journal of molecular biology,
K Sekar, and A Kumar, and X Liu, and M D Tsai, and M H Gelb, and M Sundaralingam
November 2015, Biophysical chemistry,
K Sekar, and A Kumar, and X Liu, and M D Tsai, and M H Gelb, and M Sundaralingam
April 2001, Acta crystallographica. Section D, Biological crystallography,
K Sekar, and A Kumar, and X Liu, and M D Tsai, and M H Gelb, and M Sundaralingam
January 1995, The Journal of biological chemistry,
K Sekar, and A Kumar, and X Liu, and M D Tsai, and M H Gelb, and M Sundaralingam
January 2006, Acta crystallographica. Section F, Structural biology and crystallization communications,
K Sekar, and A Kumar, and X Liu, and M D Tsai, and M H Gelb, and M Sundaralingam
January 2005, Acta crystallographica. Section F, Structural biology and crystallization communications,
Copied contents to your clipboard!