7TZ7: PI3K alpha

PI3K alpha in complex with an inhibitor. Determined by X-ray diffraction at 2.41 Å resolution. Released 18 May 2022.

Method: X-ray diffraction
Resolution: 2.41 Å
Organism: Homo sapiens
Chains: 2
Atoms: 10,019
Mol. weight: 160.63 kDa
Ligands: KVJ
Released: 18 May 2022

Explore 7TZ7 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7TZ7 contains 64 α-helices and 54 β-strands across 2 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 56 helices, 46 β-strands

Element	Residues	Length	Sheet
β-strand	10	1	1
β-strand	13	1	1
β-strand	19-25	7	2
β-strand	31-37	7	2
β-strand	41	1	3
α-helix	42-52	11
α-helix	53-55	3
α-helix	59-61	3
α-helix	65-67	3
β-strand	69-73	5	2
β-strand	74	1	4
β-strand	79-82	4	2
β-strand	88	1	3
α-helix	89-91	3
β-strand	94	1	4
β-strand	98-102	5	2
α-helix	108-121	14
α-helix	126-129	4
α-helix	134-142	9
α-helix	144-154	11
α-helix	160-166	7
β-strand	171	1	5
α-helix	179-182	4
β-strand	191-198	8	6
β-strand	203-210	8	6
α-helix	217-227	11
β-strand	254	1	7
α-helix	267-269	3
β-strand	270	1	5
α-helix	271-278	8
β-strand	285	1	7
β-strand	286-287	2	6
α-helix	290-294	5
α-helix	298-300	3
β-strand	324-326	3	8
α-helix	327-329	3
β-strand	333-341	9	9
β-strand	353-362	10	10
β-strand	365-366	2	10
β-strand	371-372	2	10
β-strand	376	1	10
β-strand	382-392	11	9
α-helix	393-395	3
β-strand	401-410	10	10
β-strand	418-428	11	10
β-strand	430	1	11
β-strand	435	1	8
β-strand	436	1	11
α-helix	437	1
β-strand	439-444	6	9
α-helix	445	1
β-strand	446	1	10
α-helix	447-449	3
α-helix	461	1
β-strand	462	1	10
β-strand	472-477	6	9
β-strand	483-485	3	8
α-helix	486-488	3
α-helix	489-500	12
α-helix	525-535	11
α-helix	545-553	9
α-helix	557-560	4
α-helix	562-564	3
α-helix	565-570	6
α-helix	577-588	12
α-helix	590-594	5
α-helix	595-598	4
α-helix	599-602	4
α-helix	609-622	14
α-helix	625-630	6
α-helix	632-637	6
α-helix	638-641	4
α-helix	648-659	12
α-helix	661-672	12
α-helix	681-694	14
α-helix	698-720	23
α-helix	728-739	12
α-helix	742-748	7
β-strand	751-753	3	12
β-strand	756-761	6	12
β-strand	764	1	13
α-helix	766-768	3
β-strand	770-771	2	13
β-strand	779-783	5	13
β-strand	797-803	7	13
α-helix	808-826	19
β-strand	838-842	5	13
β-strand	845-849	5	13
α-helix	850-851	2
β-strand	854-856	3	14
α-helix	857-860	4
α-helix	876-883	8
α-helix	889-911	23
α-helix	913-916	4
β-strand	921-924	4	14
β-strand	929-931	3	14
α-helix	958-964	7
α-helix	971-973	3
α-helix	975-993	19
α-helix	995-1003	9
α-helix	1016-1025	10
α-helix	1032-1047	16

Chain B: 8 helices, 8 β-strands

Element	Residues	Length	Sheet
β-strand	334-335	2	15
α-helix	340-347	8
α-helix	350-351	2
β-strand	354-359	6	15
β-strand	368-374	7	15
β-strand	377-383	7	15
β-strand	384-386	3	16
β-strand	389-391	3	16
α-helix	396	1
β-strand	398	1	16
α-helix	401-410	10
β-strand	426-427	2	15
α-helix	430-434	5
α-helix	442-506	65
α-helix	508-514	7
α-helix	518-587	70

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	A	protein	1074	Homo sapiens	P42336 (AlphaFold model)
Isoform 3 of Phosphatidylinositol 3-kinase regulatory subunit alpha	B	protein	291	Homo sapiens	P27986 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>7TZ7_1 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (chains A)
MPPRPSSGELWGIHLMPPRILVECLLPNGMIVTLECLREATLITIKHELFKEARKYPLHQ
LLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEPVGNREEKILNREIGFA
IGMPVCEFDMVKDPEVQDFRRNILNVCKEAVDLRDLNSPHSRAMYVYPPNVESSPELPKH
IYNKLDKGQIIVVIWVIVSPNNDKQKYTLKINHDCVPEQVIAEAIRKKTRSKKLSSEQLK
LCVLEYQGKYILKVCGCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKESLYSQLPMD
CFTMPSYSRRISTATPYMNGETSTKSLWVINSALRIKILCATYVNVNIRDIDKIYVRTGI
YHGGEPLCDNVNTQRVPCSNPRWNEWLNYDIYIPDLPRAARLCLSICSVKGRKGAKEEHC
PLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKETPCLELEFDWF
SSVVKFPDMSVIEEHANWSVSREAGFSYSHAGLSNRLARDNELRENDKEQLKAISTRDPL
SEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAME
LLDCNYPDPMVRGFAVRCLEKYLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTN
QRIGHFFFWHLKSEMHNKTVSQRFGLLLESYCRACGMYLKHLNRQVEAMEKLINLTDILK
QEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLW
LNWENPDIMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLS
IGDCVGLIEVVRNSHTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRS
CAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLDHKKKKFGYKRERVPFVLTQDF
LIVISKGAQECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDIA
YIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQHALNHHHHHH

Sequence of entity 2 (B), FASTA

>7TZ7_2 Isoform 3 of Phosphatidylinositol 3-kinase regulatory subunit alpha (chains B)
MHNLQYLPPKPPKPTTVANNGMNNNMSLQDAEWYWGDISREEVNEKLRDTADGTFLVRDA
STKMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVELINHYRNESLAQYNPKL
DVKLLYPVSKYQQDQVVKEDNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMK
RTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEKEIQRIMHNYDKLKSRISEIID
SRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQ

Ligands and cofactors

ID	Name	Formula	Copies
KVJ	(4S,5R)-3-[2'-amino-2-(morpholin-4-yl)-4'-(trifluoromethyl)[4,5'-bipyrimidin]-6…	C18 H20 F3 N7 O4	1

Primary citation

Identification of NVP-CLR457 as an Orally Bioavailable Non-CNS-Penetrant pan-Class IA Phosphoinositol-3-Kinase Inhibitor. Fairhurst, R.A., Furet, P., Imbach-Weese, P. et al. J Med Chem (2022) 65:8345-8379. DOI 10.1021/acs.jmedchem.2c00267 · PubMed

Other PDB entries of the same protein (UniProt P42336 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9CMK 1.75 Å, Crystal structure of p110alpha-RAS binding domain (RBD) in complex with molecular glue…
9ASF 1.77 Å, Crystal structure of HLA-A*03:01 in complex with a wild-type PIK3CA peptide analogue…
9CX0 1.92 Å, Crystal structure of HLA-A*03:01 E152V mutant in complex with a mutant PIK3CA peptide
7L1C 1.96 Å, Crystal structure of HLA-A*03:01 in complex with a mutant PIK3CA peptide
9CWY 1.98 Å, Crystal structure of HLA-A*03:02 in complex with a wild-type PIK3CA peptide
8EXL 1.99 Å, Crystal structure of PI3K-alpha in complex with taselisib
9CX1 2.0 Å, Crystal structure of HLA-A*03:01 L156Q mutant in complex with a mutant PIK3CA peptide
9CML 2.01 Å, Crystal structure of p110alpha-RAS binding domain (RBD) in complex with molecular glue…
9ASG 2.03 Å, Crystal structure of HLA-A*03:01 in complex with a mutant PIK3CA peptide analogue (Trp-6…
7L1B 2.04 Å, Crystal structure of HLA-A*03:01 in complex with a wild-type PIK3CA peptide
9CWZ 2.05 Å, Crystal structure of HLA-A*03:02 in complex with a mutant PIK3CA peptide
7JIU 2.12 Å, Human PI3KDELTA in complex with compound 2F

Browse structure collections

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