4WAF: PDB entry 4WAF

Crystal Structure of a novel tetrahydropyrazolo[1,5-a]pyrazine in an engineered PI3K alpha. Determined by X-ray diffraction at 2.39 Å resolution. Released 31 Dec 2014.

Method: X-ray diffraction
Resolution: 2.39 Å
Organism: Homo sapiens
Chains: 2
Atoms: 10,388
Mol. weight: 164.31 kDa
Ligands: 3K6
Released: 31 Dec 2014

Explore 4WAF in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

4WAF contains 63 α-helices and 50 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: 57 helices, 45 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	126-130	5
α-helix	134-142	9
α-helix	144-154	11
α-helix	160-166	7
β-strand	171	1	5
α-helix	176-178	3
α-helix	179-182	4
β-strand	189-198	10	6
β-strand	203-212	10	6
α-helix	217-226	10
α-helix	237-242	6
β-strand	250-254	5	6
β-strand	260-261	2	6
α-helix	267-269	3
β-strand	270	1	5
α-helix	271-279	9
α-helix	281-283	3
β-strand	284-289	6	6
α-helix	290-294	5
α-helix	298-300	3
α-helix	306-309	4
β-strand	324-326	3	7
α-helix	327-329	3
β-strand	333-341	9	8
β-strand	353-362	10	9
β-strand	365-366	2	9
β-strand	371-372	2	9
β-strand	376	1	9
β-strand	382-392	11	8
α-helix	393-395	3
β-strand	401-413	13	9
β-strand	416-428	13	9
β-strand	430	1	10
β-strand	435	1	7
β-strand	436	1	10
α-helix	437	1
β-strand	439-444	6	8
β-strand	446	1	9
α-helix	447-449	3
β-strand	472-477	6	8
β-strand	483-485	3	7
α-helix	486-488	3
α-helix	489-499	11
α-helix	526-536	11
α-helix	545-553	9
α-helix	558-560	3
α-helix	562-564	3
α-helix	565-571	7
α-helix	577-588	12
α-helix	590-592	3
α-helix	595-598	4
α-helix	599-602	4
α-helix	609-622	14
α-helix	625-637	13
α-helix	638-641	4
α-helix	648-657	10
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	751-752	2	11
β-strand	760-761	2	11
β-strand	764	1	12
α-helix	766-768	3
β-strand	770-771	2	12
β-strand	779-784	6	12
α-helix	790-792	3
β-strand	796-803	8	12
α-helix	808-826	19
α-helix	835-837	3
β-strand	838-842	5	12
β-strand	845-849	5	12
β-strand	854-856	3	13
α-helix	857-863	7
α-helix	876-884	9
α-helix	887-889	3
α-helix	890-911	22
β-strand	921-924	4	13
β-strand	929-931	3	13
α-helix	958-964	7
α-helix	975-993	19
α-helix	995-1004	10
α-helix	1016-1025	10
α-helix	1032-1047	16

Chain B: 6 helices, 5 β-strands

Element	Residues	Length	Sheet
β-strand	334-336	3	14
α-helix	340-347	8
α-helix	350-351	2
β-strand	355-359	5	14
β-strand	368-374	7	14
β-strand	377-383	7	14
α-helix	401-410	10
β-strand	427	1	14
α-helix	433-436	4
α-helix	442-514	73
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	1073	Homo sapiens	P42336 (AlphaFold model)
Phosphatidylinositol 3-kinase regulatory subunit alpha	B	protein	323	Homo sapiens	P27986 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>4WAF_1 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (chains A)
PPRPSSGELWGIHLMPPRILVECLLPNGMIVTLECLREATLITIKHELFKEARKYPLHQL
LQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEPVGNREEKILNREIGFAI
GMPVCEFDMVKDPEVQDFRRNILNVCKEAVDLRDLNSPHSRAMYVYPPNVESSPELPKHI
YNKLDKGQIIVVIWVIVSPNNDKQKYTLKINHDCVPEQVIAEAIRKKTRSKKLSSEQLKL
CVLEYQGKYILKVCGCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKESLYSQLPMDC
FTMPSYSRRISTATPYMNGETSTKSLWVINSALRIKILCATYVNVNIRDIDKIYVRTGIY
HGGEPLCDNVNTQRVPCSNPRWNEWLNYDIYIPDLPRAARLCLSICSVKGRKGAKEEHCP
LAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKETPCLELEFDWFS
SVVKFPDMSVIEEHANWSVSREAGFSYSHAGLSNRLARDNELRENDKEQLKAISTRDPLS
EITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAMEL
LDCNYPDPMVRGFAVRCLEKYLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTNQ
RIGHFFFWHLKSEMHNKTVSQRFGLLLESYCRACGMYLKHLNRQVEAMEKLINLTDILKQ
EKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLWL
NWENPDIMSELLFQNNEIMFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSI
GDCVGLIEVVRNSHTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSC
AGYCVATFILGIGDRHNSNIMVKDDGQLVHIDFGHFLDHKKKKFGYKRERVPFVLTQDFL
IVISKGAQECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDIAY
IRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQHALNHHHHHH

Sequence of entity 2 (B), FASTA

>4WAF_2 Phosphatidylinositol 3-kinase regulatory subunit alpha (chains B)
MEYMPMEHNLQYLPPKPPKPTTVANNGMNNNMSLQDAEWYWGDISREEVNEKLRDTADGT
FLVRDASTKMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVELINHYRNESLA
QYNPKLDVKLLYPVSKYQQDQVVKEDNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTS
QEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEKEIQRIMHNYDKLKSR
ISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQKKL
NEWLGNENTEDQYSLVEDDEDLP

Ligands and cofactors

ID	Name	Formula	Copies
3K6	N,N-dimethyl-4-[(6R)-6-methyl-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-4,5,6,7-tetrahy…	C22 H24 N6 O2 S	1

Primary citation

Structure-Based Drug Design of Novel Potent and Selective Tetrahydropyrazolo[1,5-a]pyrazines as ATR Inhibitors. Barsanti, P.A., Aversa, R.J., Jin, X. et al. ACS Med Chem Lett (2015) 6:37-41. DOI 10.1021/ml500353p · 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

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