PrionDB: Extraction of mutation data from the literature

2005, PrionDB.

This data was extracted from Medline abstracts and full texts (when available) in an automated manner.

The table below describes the selected point mutation and provides links to other documents. The sentence(s) where the point mutation E199K was found are listed after the table.

The mutated residues are also indicated in the family sequence alignments and hyperlinked to the corresponding mutation pages.

Point mutation E199K in PRIO_MOUSE

Point mutation:	E199K
Cited point mutation:	E200K,Glu200Lys,Glu200
Domain:	Not determined
General numbering (PrionDB):	-
Protein:	PRIO_MOUSE (Prnp,Prn-p)	Swiss-Prot Cross-reference table Family page
Other point mutations / same protein / same position	Point mutations at position 199 in PRIO_MOUSE
Other point mutations / same protein	List of mutations in PRIO_MOUSE
Family alignments	Mammalian prion proteins Prion proteins (PRP, PRNP)
Other point mutations / same position	Position 200 in Mammalian prion proteins family Position 200 in Prion proteins (PRP, PRNP) family
Reference:	Influence of amino acid substitutions related to inherited human prion diseases on the thermodynamic stability of the cellular prion protein. Liemann S, Glockshuber R Biochemistry 1999 Mar 16;38(11):3258-67.	Medline
Other point mutations / same article	List
Text source	HTML and PDF full texts
Validation status	True positive

Relevant sentences:

E200K

------------------------------------------------------------------------ Table 1: Thermodynamic Stabilities of mPrP(121-231) Variants , mPrP(121-231) Wild Type , and Full-Length mPrP(23-231) Wild Type at pH 7.0 and 25 (image)C mPrP protein prion disease phenotype (image)G(image) fold (kJ mol-1)a (image)(image)G(image) fold (variant - wild type) b cooperativity (kJ mol-1 M-1)a [urea]1 / 2 (M) a mPrP(121-231) wt -29.7 ą 1.0 4.8 ą 0.2 6.2 mPrP(23-231) wt -25.5 ą 1.0 4.2 ą 1.9 4.1 ą 0.2 6.3 M129V polymorphism (human) -28.2 ą 1.0 1.4 ą 2.0 4.5 ą 0.2 6.3 D178N / M129 FFI -22.5 ą 0.7 7.2 ą 1.7 4.7 ą 0.1 4.8 D178N / V129 CJD -21.7 ą 0.9 8.0 ą 1.8 4.5 ą 0.2 4.9 V180I GSS -27.6 ą 0.8 2.1 ą 1.7 4.5 ą 0.1 6.2 T183A CJD -10.4 ą 2.1 19.3 ą 3.1 3.5 ą 0.5 3.0 T190V polymorphism (mouse) -30.3 ą 1.5 -0.7 ą 2.4 4.8 ą 0.2 6.4 F198S GSS -19.4 ą 0.8 10.3 ą 1.7 4.4 ą 0.2 4.5 E200K CJD -29.1 ą 1.5 0.6 ą 2.4 4.9 ą 0.3 5.9 R208H CJD -23.7 ą 1.5 6.0 ą 2.5 4.3 ą 0.3 5.6 V210I CJD -28.6 ą 1.6 1.1 ą 2.6 4.5 ą 0.3 6.3 Q217R GSS -20.8 ą 0.8 8.9 ą 1.7 4.5 ą 0.2 4.7 a The thermodynamic stabilities were measured by urea-induced equilibrium transitions (Figure 5)
Table 1: Thermodynamic Stabilities of mPrP(121-231) Variants , mPrP(121-231) Wild Type , and Full-Length mPrP(23-231) Wild Type at pH 7.0 and 25 °C mPrP protein prion disease phenotype G°fold (kJ mol-1)a G°fold (variant - wild type)b cooperativity (kJ mol-1 M-1)a [urea]1 / 2 (M)a mPrP(121-231) wt - -29.7 ( 1.0 - 4.8 ( 0.2 6.2 mPrP(23-231) wt - -25.5 ( 1.0 4.2 ( 1.9 4.1 ( 0.2 6.3 M129V polymorphism (human) -28.2 ( 1.0 1.4 ( 2.0 4.5 ( 0.2 6.3 D178N / M129 FFI -22.5 ( 0.7 7.2 ( 1.7 4.7 ( 0.1 4.8 D178N / V129 CJD -21.7 ( 0.9 8.0 ( 1.8 4.5 ( 0.2 4.9 V180I GSS -27.6 ( 0.8 2.1 ( 1.7 4.5 ( 0.1 6.2 T183A CJD -10.4 ( 2.1 19.3 ( 3.1 3.5 ( 0.5 3.0 T190V polymorphism (mouse) -30.3 ( 1.5 -0.7 ( 2.4 4.8 ( 0.2 6.4 F198S GSS -19.4 ( 0.8 10.3 ( 1.7 4.4 ( 0.2 4.5 E200K CJD -29.1 ( 1.5 0.6 ( 2.4 4.9 ( 0.3 5.9 R208H CJD -23.7 ( 1.5 6.0 ( 2.5 4.3 ( 0.3 5.6 V210I CJD -28.6 ( 1.6 1.1 ( 2.6 4.5 ( 0.3 6.3 Q217R GSS -20.8 ( 0.8 8.9 ( 1.7 4.5 ( 0.2 4.7 a The thermodynamic stabilities were measured by urea-induced equilibrium transitions (Figure 5)

Glu200Lys

Lane 1 , molecular mass standards ; 2 , wild-type mPrP(121-231) before induction with IPTG ; 3 , wild-type mPrP(121-231) 18 h after induction (same as for the variants shown in the following lanes) ; 4 , Met129Val ; 5 , Met129 / Asp178Asn ; 6 , Met129Val / Asp178Asn ; 7 , Val180Ile ; 8 , Thr183Ala ; 9 , Thr190Val ; 10 , Phe198Ser ; 11 , Glu200Lys ; 12 , Arg208His ; 13 , Val210Ile ; 14 , Gln217Arg
Like mPrP(121-231) wild type (37) , the TSE-related variants Val180Ile , Glu200Lys , Arg208His , and Val210Ile as well the polymorphism variants Met129Val and Thr190Val were produced as soluble proteins in the periplasm of E
Both polymorphism variants Met129Val and Thr190Val as well as the TSE-related variants Glu200Lys and Val210Ile have the same stability as mPrP(121-231) wild type within experimental error ((image)G(image)fold ~ -29 kJ mol-1 ; Table 1)
In contrast to our results , the hPrP(90-231) Glu200Lys variant had a slightly destabilizing effect (50)
The mPrP variants Pro102Leu , Asp178Asn / Met129 , Thr183Ala , and Glu200Lys (numbering according to human PrP) and a protein with an insertion of six additional octapeptide repeats displayed a number of biochemical hallmarks characteristic of PrP Sc such as detergent insolubility , protease resistance , aberrant membrane attachment , and hydrophobicity
For example , the observation that the amino acid replacement Val210Ile has no effect on the intrinsic stability of mPrP(121-231) suggests similar tendencies of wild type and mutant PrP C to be converted into PrP Sc (89) , but in case of the exchange Glu200Lys , which does not affect the stability either , only the mutant PrP is converted into the protease-resistant form (87)
This view is supported by the findings that mice overexpressing a murine PrP transgene with the human GSS mutation Pro102Leu , which is assumed to be nondestabilizing for PrP C , spontaneously develop a lethal and infectious scrapie-like disease (90 , 91) , whereas the nondestabilizing Glu200Lys mutation did not cause a TSE-like illness (92)
Both polymorphism variants Met129Val and Thr190Val as well as the TSE-related variants Glu200Lys and Val210Ile have the same stability as mPrP(121-231) wild type within experimental error ( G°fold -29 kJ mol-1 ; Table 1)

Glu200

Lane 1 , molecular mass standards ; 2 , wild-type mPrP(121-231) before induction with IPTG ; 3 , wild-type mPrP(121-231) 18 h after induction (same as for the variants shown in the following lanes) ; 4 , Met129Val ; 5 , Met129 / Asp178Asn ; 6 , Met129Val / Asp178Asn ; 7 , Val180Ile ; 8 , Thr183Ala ; 9 , Thr190Val ; 10 , Phe198Ser ; 11 , Glu200Lys ; 12 , Arg208His ; 13 , Val210Ile ; 14 , Gln217Arg
Like mPrP(121-231) wild type (37) , the TSE-related variants Val180Ile , Glu200Lys , Arg208His , and Val210Ile as well the polymorphism variants Met129Val and Thr190Val were produced as soluble proteins in the periplasm of E
Both polymorphism variants Met129Val and Thr190Val as well as the TSE-related variants Glu200Lys and Val210Ile have the same stability as mPrP(121-231) wild type within experimental error ((image)G(image)fold ~ -29 kJ mol-1 ; Table 1)
In contrast to our results , the hPrP(90-231) Glu200Lys variant had a slightly destabilizing effect (50)
Surprisingly , the substitution of Glu200 by Lys at the N-terminus of helix 3 does not alter the thermodynamic stability , although an unfavorable interaction of the positively charged lysine side chain with the helix dipole seems possible (53 , 59)
The mPrP variants Pro102Leu , Asp178Asn / Met129 , Thr183Ala , and Glu200Lys (numbering according to human PrP) and a protein with an insertion of six additional octapeptide repeats displayed a number of biochemical hallmarks characteristic of PrP Sc such as detergent insolubility , protease resistance , aberrant membrane attachment , and hydrophobicity
For example , the observation that the amino acid replacement Val210Ile has no effect on the intrinsic stability of mPrP(121-231) suggests similar tendencies of wild type and mutant PrP C to be converted into PrP Sc (89) , but in case of the exchange Glu200Lys , which does not affect the stability either , only the mutant PrP is converted into the protease-resistant form (87)
This view is supported by the findings that mice overexpressing a murine PrP transgene with the human GSS mutation Pro102Leu , which is assumed to be nondestabilizing for PrP C , spontaneously develop a lethal and infectious scrapie-like disease (90 , 91) , whereas the nondestabilizing Glu200Lys mutation did not cause a TSE-like illness (92)
Both polymorphism variants Met129Val and Thr190Val as well as the TSE-related variants Glu200Lys and Val210Ile have the same stability as mPrP(121-231) wild type within experimental error ( G°fold -29 kJ mol-1 ; Table 1)
Surprisingly , the substitution of Glu200 by Lys at the N-terminus of helix -->does not alter the thermodynamic stability , although an unfavorable interaction of the positively charged lysine side chain with the helix dipole seems possible (53 , 59)

F.Horn (priondbcmbi.ru.nl), 22-Aug-2005