A molecular model of a point mutation (Val297Met) in the serine protease domain of protein C.
- Author:
Kyung Soon SONG
1
;
Young Sook PARK
;
Jong Rak CHOI
;
Hyun Kyung KIM
;
Quehn PARK
Author Information
1. Department of Clinical Pathology, College of Medicine, Yonsei University, Seoul, Korea. kssong@yumc.yonsei.ac.kr
- Publication Type:Original Article
- Keywords:
protein C deficiency;
deep vein thrombosis;
polymerase chain reaction (PCR);
direct sequencing;
point mutation;
protein modeling
- MeSH:
Adult;
Base Sequence;
Female;
Human;
Male;
Middle Age;
Models, Molecular*;
Molecular Sequence Data;
Pedigree;
Point Mutation*;
Polymerase Chain Reaction/methods;
Protein C/genetics*;
Protein C/chemistry*;
Protein C Deficiency/genetics*;
Protein Conformation;
Serine Endopeptidases/genetics;
Serine Endopeptidases/chemistry*;
Venous Thrombosis/genetics
- From:Experimental & Molecular Medicine
1999;31(1):47-51
- CountryRepublic of Korea
- Language:English
-
Abstract:
A heterozygous GTG to ATG (Val297Met) mutation was detected in a patient with inherited protein C deficiency and deep vein thrombosis. Cosegregation of the mutation with protein C deficiency was observed through a family pedigree study. Molecular models of the serine protease domains of wild type and mutant protein C were constructed by standard comparative method. Val 297 was found to be located in the hydrophobic core of the protein. Although the substitution of Met for Val does not greatly alter the hydrophobicity of the protein, it introduces a bulkier side chain, which yields steric hindrance between this residue and adjacent residues, such as Met364, Tyr393, Ile321, Ile323, and Val378. It seems that the Met can not fit into the tight packing into which it is trapped, thereby probably inducing misfolding and/or greater instability of the protein. Such misfolding and/or instability thereby eventually disturbs the catalytic triad, in consistent with the observed type I deficiency state.
