Regulation of Human Cytochrome P4501A1 (hCYP1A1): A Plausible Target for Chemoprevention?

Table 2

Effect of mutations in the amino acid sequence of human CYP1A1 on the kinetic parameters of this enzyme.

Amino acid	Position	Amino acid type	Mutation	Amino acid type	Effect	Reference
Gly	45; loop A′	Nonpolar, aliphatic	Asp	Negatively charged	and are decreased by 42.9% and 75.1%, respectively	[75]
Ala	62; helix A	Nonpolar, aliphatic	Pro	Nonpolar, aliphatic	is increased by 84% and is decreased by 21%	[76]
Ser	116; helix B′	Polar, uncharged	Ala	Nonpolar, aliphatic	and do not change	[77]
Ser	122; loop B′-C	Polar, uncharged	Thr	Polar, uncharged	Activity is increased by 25%	[78]
			Ala	Nonpolar, aliphatic	and are increased by 74% and 2-fold, respectively	[79]
Phe	123; loop B′-C	Aromatic	Ala	Nonpolar, aliphatic	Without activity.; is increased by 12.8-fold and is decreased by 42.5%	[77, 79]
Glu	161; helix D	Negatively charged	Lys	Positively charged	is decreased by 39% and does not change	[77]
Glu	166; helix D	Negatively charged	Gln	Nonpolar, aliphatic	and are increased by 3.7-fold and 24%, respectively	[77]
Val	191; helix E	Nonpolar, aliphatic	Met	Polar, uncharged	and do not change	[77]
Asn	221; helix F	Nonpolar, aliphatic	Thr	Polar, uncharged	Activity is decreased to 28%	[78]
Phe	224; helix F	Aromatic	Ala	Nonpolar, aliphatic	and are decreased by 11.4-fold and 75%, respectively	[79]
Gly	225; helix F	Nonpolar, aliphatic	Val	Nonpolar, aliphatic	Activity is decreased to 19%	[78]
Val	228; helix F	Nonpolar, aliphatic	Thr	Polar, uncharged	and do not change	[77]
Glu	256; helix G	Negatively charged	Lys	Positively charged	is decreased by 70% and does not change	[77]
Tyr	259; helix G	Aromatic	Phe	Aromatic	is increased by 2.7-fold and does not change	[77]
Asn	309; helix H	Nonpolar, aliphatic	Thr	Polar, uncharged	and do not change	[77]
Leu	312; helix I	Nonpolar, aliphatic	Asn	Nonpolar, aliphatic	Activity is decreased to 42%	[78]
			Phe	Aromatic	is increased by 89% and does not change	[77]
Asp	313; helix I	Negatively charged	Ala	Nonpolar, aliphatic	and are increased by 21-fold and 28%, respectively	[77]
			Asn	Nonpolar, aliphatic	is increased by 24.5-fold and is decreased by 37.5%	[77]
Gly	316; helix I	Nonpolar, aliphatic	Val	Nonpolar, aliphatic	is increased by 17-fold and is decreased by 30%	[77]
Ala	317; helix I	Nonpolar, aliphatic	Tyr	Aromatic	Without activity	[79]
			Gly	Nonpolar, aliphatic	is increased by 30-fold and is decreased by 25%	[77]
Asp	320; helix I	Negatively charged	Ala	Nonpolar, aliphatic	is increased by 2.7-fold and is decreased by 35%	[77]
Thr	321; helix I	Polar, uncharged	Gly	Nonpolar, aliphatic	is increased by 30% and is decreased by 70%	[79]
			Pro	Nonpolar, aliphatic	is increased by 6.2-fold and does not change	[77]
			Ser	Polar, uncharged	and are increased by 7.6-fold and 2-fold, respectively	[77]
Val	322; helix I	Nonpolar, aliphatic	Ala	Nonpolar, aliphatic	is increased by 67% and does not change	[77]
Val	382; helix K/ loop β1–4	Nonpolar, aliphatic	Ala	Nonpolar, aliphatic	Activity is decreased to 66%	[78]
			Leu	Nonpolar, aliphatic	Activity is decreased to 7%	[78]
Ile	386; helix K/ loop β1–4	Nonpolar, aliphatic	Gly	Nonpolar, aliphatic	Without activity	[79]
			Val	Nonpolar, aliphatic	and are increased by 87% and 58%, respectively	[77]
Ile	458; helix L	Nonpolar, aliphatic	Pro	Nonpolar, aliphatic	is increased by 44% and does not change	[77]
			Val	Nonpolar, aliphatic	and are decreased by 55% and 21%, respectively	[77]
Thr	497; loop β4	Polar, uncharged	Ser	Polar, uncharged	is increased by 3-fold and does not change	[77]