5AAV

Optimization of a novel binding motif to to (E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H- pyrido(3,4-b)indol-1-yl)phenyl)acrylic acid (AZD9496), a potent and orally bioavailable selective estrogen receptor downregulator and antagonist

Entity

Entity ID	Chain ID	Description	Type	Chain length	Formula weight	Number of molecules	DB Name (Accession)	Biological source	Descriptive keywords
1	A (A)	ESTROGEN RECEPTOR	polymer	252	28655.5	1	UniProt (P03372) Pfam (PF00104)	HOMO SAPIENS (HUMAN)	ER, ER-ALPHA, ESTRADIOL RECEPTOR, NUCLEAR RECEPTOR SUBFAMILY 3 GROUP A MEMBER 1, ESTROGEN RECEPTOR ALPHA
2	B (B)	ESTROGEN RECEPTOR	polymer	252	28637.5	1	UniProt (P03372) Pfam (PF00104)	HOMO SAPIENS (HUMAN)	ER, ER-ALPHA, ESTRADIOL RECEPTOR, NUCLEAR RECEPTOR SUBFAMILY 3 GROUP A MEMBER 1, ESTROGEN RECEPTOR ALPHA
3	C, D (A, B)	(2E)-3-{4-[(1E)-1,2-DIPHENYLBUT-1-ENYL]PHENYL}ACRYLIC ACID	non-polymer		354.4	2	Chemie (GW5)
4	E, F (A, B)	water	water		18.0	166	Chemie (HOH)

Sequence modifications

A: 307 - 554 (UniProt: P03372)

PDB	External Database	Details
Gly 303	-	expression tag
Ser 304	-	expression tag
His 305	-	expression tag
Met 306	-	expression tag
Ser 381	Cys 381	engineered mutation
Ser 417	Cys 417	engineered mutation
Ser 530	Cys 530	engineered mutation
Ser 536	Leu 536	engineered mutation

B: 306 - 554 (UniProt: P03372)

PDB	External Database	Details
Gly 303	-	expression tag
Ser 304	-	expression tag
His 305	-	expression tag
Ser 381	Cys 381	engineered mutation
Ser 417	Cys 417	engineered mutation
Ser 530	Cys 530	engineered mutation
Ser 536	Leu 536	engineered mutation

Contents of the asymmetric unit

Polymers	Number of chains	2
	Total formula weight	57293.0
Non-Polymers*	Number of molecules	2
	Total formula weight	708.9
All*	Total formula weight	58001.9

*Water molecules are not included.