Three-dimensional structures of human phospholipase A2 from pancreas and synovial fluid by model building

I T Christensen; Flemming Steen Jørgensen; L A Svensson; T Högberg

Three-dimensional structures of human phospholipase A2 from pancreas and synovial fluid by model building

I T Christensen, Flemming Steen Jørgensen, L A Svensson, T Högberg

5 Citations (Scopus)

Abstract

Three-dimensional structures of the enzyme phospholipase A2 (PLA2) from human pancreas and from human synovial fluid were constructed by model building based on high-resolution X-ray crystallographic structures and homology considerations. The structure of the human pancreatic PLA2 was based on the X-ray structure of the highly homologous bovine pancreatic PLA2 (Type I) by amino acid substitution and modification of the C-terminal part followed by geometry relaxation. The structure of the PLA2 from human synovial fluid was constructed from the X-ray structure of PLA2 from Crotalus atrox (Type II) by modification of the calcium binding loop, amino acid substitution, and insertion of two additional amino acid residues followed by geometry relaxation. The structure of the two human PLA2's have been compared and their use as targets for rational design of enzyme inhibitors discussed.

Original language	English
Journal	Drug Design and Discovery
Volume	10
Issue number	2
Pages (from-to)	101-13
Number of pages	13
ISSN	1055-9612
Publication status	Published - 1993

Keywords

Amino Acid Sequence
Animals
Binding Sites
Calcium
Crotalus
Humans
Models, Molecular
Molecular Sequence Data
Pancreas
Phospholipases A
Phospholipases A2
Protein Conformation
Sequence Alignment
Synovial Fluid
Thermodynamics

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Cite this

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title = "Three-dimensional structures of human phospholipase A2 from pancreas and synovial fluid by model building",

abstract = "Three-dimensional structures of the enzyme phospholipase A2 (PLA2) from human pancreas and from human synovial fluid were constructed by model building based on high-resolution X-ray crystallographic structures and homology considerations. The structure of the human pancreatic PLA2 was based on the X-ray structure of the highly homologous bovine pancreatic PLA2 (Type I) by amino acid substitution and modification of the C-terminal part followed by geometry relaxation. The structure of the PLA2 from human synovial fluid was constructed from the X-ray structure of PLA2 from Crotalus atrox (Type II) by modification of the calcium binding loop, amino acid substitution, and insertion of two additional amino acid residues followed by geometry relaxation. The structure of the two human PLA2's have been compared and their use as targets for rational design of enzyme inhibitors discussed.",

keywords = "Amino Acid Sequence, Animals, Binding Sites, Calcium, Crotalus, Humans, Models, Molecular, Molecular Sequence Data, Pancreas, Phospholipases A, Phospholipases A2, Protein Conformation, Sequence Alignment, Synovial Fluid, Thermodynamics",

author = "Christensen, {I T} and J{\o}rgensen, {Flemming Steen} and Svensson, {L A} and T H{\"o}gberg",

year = "1993",

language = "English",

volume = "10",

pages = "101--13",

journal = "Drug Design and Discovery",

issn = "1055-9612",

publisher = "Taylor & Francis",

number = "2",

}

TY - JOUR

T1 - Three-dimensional structures of human phospholipase A2 from pancreas and synovial fluid by model building

AU - Christensen, I T

AU - Jørgensen, Flemming Steen

AU - Svensson, L A

AU - Högberg, T

PY - 1993

Y1 - 1993

N2 - Three-dimensional structures of the enzyme phospholipase A2 (PLA2) from human pancreas and from human synovial fluid were constructed by model building based on high-resolution X-ray crystallographic structures and homology considerations. The structure of the human pancreatic PLA2 was based on the X-ray structure of the highly homologous bovine pancreatic PLA2 (Type I) by amino acid substitution and modification of the C-terminal part followed by geometry relaxation. The structure of the PLA2 from human synovial fluid was constructed from the X-ray structure of PLA2 from Crotalus atrox (Type II) by modification of the calcium binding loop, amino acid substitution, and insertion of two additional amino acid residues followed by geometry relaxation. The structure of the two human PLA2's have been compared and their use as targets for rational design of enzyme inhibitors discussed.

AB - Three-dimensional structures of the enzyme phospholipase A2 (PLA2) from human pancreas and from human synovial fluid were constructed by model building based on high-resolution X-ray crystallographic structures and homology considerations. The structure of the human pancreatic PLA2 was based on the X-ray structure of the highly homologous bovine pancreatic PLA2 (Type I) by amino acid substitution and modification of the C-terminal part followed by geometry relaxation. The structure of the PLA2 from human synovial fluid was constructed from the X-ray structure of PLA2 from Crotalus atrox (Type II) by modification of the calcium binding loop, amino acid substitution, and insertion of two additional amino acid residues followed by geometry relaxation. The structure of the two human PLA2's have been compared and their use as targets for rational design of enzyme inhibitors discussed.

KW - Amino Acid Sequence

KW - Animals

KW - Binding Sites

KW - Calcium

KW - Crotalus

KW - Humans

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Pancreas

KW - Phospholipases A

KW - Phospholipases A2

KW - Protein Conformation

KW - Sequence Alignment

KW - Synovial Fluid

KW - Thermodynamics

M3 - Journal article

C2 - 8399996

SN - 1055-9612

VL - 10

SP - 101

EP - 113

JO - Drug Design and Discovery

JF - Drug Design and Discovery

IS - 2

ER -

Three-dimensional structures of human phospholipase A2 from pancreas and synovial fluid by model building

Abstract

Keywords

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