7RCT: Non-receptor Protein Tyrosine Phosphatase SHP2

Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor RMC-4550. Determined by X-ray diffraction at 1.8 Å resolution. Released 1 Sept 2021.

Method: X-ray diffraction
Resolution: 1.8 Å
Organism: Homo sapiens
Chains: 2
Atoms: 8,806
Mol. weight: 121.44 kDa
Ligands: 4Q4
Released: 1 Sept 2021

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

Secondary structure: helices and β-sheets

7RCT contains 40 α-helices and 60 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: 20 helices, 28 β-strands

Element	Residues	Length	Sheet
β-strand	7	1	9
α-helix	13-23	11
β-strand	28-33	6	9
β-strand	41-47	7	9
β-strand	50-57	8	9
β-strand	63-65	3	9
β-strand	70-71	2	9
α-helix	74-83	10
β-strand	100-101	2	9
β-strand	113	1	10
α-helix	119-129	11
β-strand	134-139	6	10
β-strand	147-154	8	10
β-strand	165-172	8	10
β-strand	173-175	3	11
β-strand	178-180	3	11
β-strand	187	1	11
α-helix	190-199	10
β-strand	202-203	2	12
β-strand	209-210	2	12
β-strand	214-215	2	10
β-strand	221-222	2	13
α-helix	223-225	3
α-helix	226-234	9
α-helix	246-256	11
α-helix	257-261	5
α-helix	266-269	4
α-helix	271-276	6
β-strand	289-291	3	14
α-helix	292-293	2
β-strand	304-310	7	14
β-strand	327-330	4	14
α-helix	331-334	4
α-helix	335-337	3
α-helix	338-347	10
β-strand	352-355	4	14
α-helix	372-373	2
β-strand	377-380	4	14
β-strand	383-392	10	14
β-strand	396-405	10	14
β-strand	408-420	13	14
α-helix	433-447	15
α-helix	454	1
β-strand	455-458	4	14
α-helix	465-482	18
β-strand	487-488	2	13
α-helix	490-498	9
α-helix	508-523	16

Chain B: 20 helices, 32 β-strands

Element	Residues	Length	Sheet
β-strand	7	1	1
α-helix	13-23	11
β-strand	28-33	6	1
β-strand	40-47	8	1
β-strand	50-57	8	1
β-strand	63-65	3	1
β-strand	70-71	2	1
α-helix	74-83	10
β-strand	89	1	2
β-strand	95	1	2
β-strand	100-101	2	1
β-strand	113	1	3
α-helix	119-129	11
β-strand	134-139	6	3
β-strand	147-154	8	3
β-strand	165-172	8	3
β-strand	173-175	3	4
β-strand	178-180	3	4
β-strand	187	1	4
α-helix	190-199	10
β-strand	202-203	2	5
β-strand	209-210	2	5
β-strand	214-215	2	3
β-strand	221-222	2	6
α-helix	223-225	3
α-helix	226-234	9
α-helix	246-256	11
α-helix	257-261	5
α-helix	267-269	3
α-helix	271-276	6
β-strand	289	1	7
α-helix	290-292	3
β-strand	307-310	4	7
β-strand	327-330	4	7
α-helix	331-334	4
α-helix	335-337	3
α-helix	338-347	10
β-strand	352-355	4	7
β-strand	360-361	2	8
β-strand	364-365	2	8
α-helix	372-373	2
β-strand	377-380	4	7
β-strand	383-392	10	7
β-strand	396-405	10	7
β-strand	408-420	13	7
α-helix	433-447	15
α-helix	454	1
β-strand	455-458	4	7
α-helix	464-482	19
β-strand	487-488	2	6
α-helix	490-498	9
α-helix	508-523	16

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Tyrosine-protein phosphatase non-receptor type 11	A, B	protein	525	Homo sapiens	Q06124 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>7RCT_1 Tyrosine-protein phosphatase non-receptor type 11 (chains A, B)
MTSRRWFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTG
DYYDLYGGEKFATLAELVQYYMEHHGQLKEKNGDVIELKYPLNCADPTSERWFHGHLSGK
EAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTGDDKGESNDGKSKVTHVMIRCQELKYD
VGGGERFDSLTDLVEHYKKNPMVETLGTVLQLKQPLNTTRINAAEIESRVRELSKLAETT
DKVKQGFWEEFETLQQQECKLLYSRKEGQRQENKNKNRYKNILPFDHTRVVLHDGDPNEP
VSDYINANIIMPEFETKCNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEV
ERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTERTVWQYHF
RTWPDHGVPSDPGGVLDFLEEVHHKQESIMDAGPVVVHCSAGIGRTGTFIVIDILIDIIR
EKGVDCDIDVPKTIQMVRSQRSGMVQTEAQYRFIYMAVQHYIETL

Ligands and cofactors

ID	Name	Formula	Copies
4Q4	{3-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl]-6-(2,3-dichloroph…	C21 H26 Cl2 N4 O2	2

Water and common crystallization additives (CL) are not listed.

Primary citation

Targeted Degradation of the Oncogenic Phosphatase SHP2. Vemulapalli, V., Donovan, K.A., Seegar, T.C.M. et al. Biochemistry (2021) 60:2593-2609. DOI 10.1021/acs.biochem.1c00377 · PubMed

Other PDB entries of the same protein (UniProt Q06124 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9EIK 1.25 Å, Crystal structure of N-SH2 domain of SHP2 with T42A mutation bound to GAB1 tyrosine…
3ZM1 1.4 Å, Catalytic domain of human SHP2
4JMG 1.4 Å, Crystal structure of the synthetic protein in complex with pY peptide
7PPM 1.48 Å, SHP2 catalytic domain in complex with IRS1 (889-901) phosphopeptide (pSer-892, pTyr-896)
3ZM0 1.5 Å, Catalytic domain of human SHP2
3ZM2 1.5 Å, Catalytic domain of human SHP2
3ZM3 1.5 Å, Catalytic domain of human SHP2
7PPL 1.53 Å, SHP2 catalytic domain in complex with IRS1 (625-639) phosphopeptide (pTyr-632, pSer-636)
9EIC 1.58 Å, Crystal structure of unbound N-SH2 domain of SHP2 with T42A mutation
9EHD 1.59 Å, Crystal structure of N-SH2 domain of SHP2 bound to GAB1 tyrosine phosphorylated peptide…
3B7O 1.6 Å, Crystal structure of the human tyrosine phosphatase SHP2 (PTPN11) with an accessible…
4RDD 1.6 Å, Co-crystal structure of SHP2 in complex with a Cefsulodin derivative

Browse structure collections

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