6V9J: GTPase HRas

Expanding the Chemical Landscape of SOS1 Activators Using Fragment Based Methods. Determined by X-ray diffraction at 1.76 Å resolution. Released 26 Aug 2020.

Method: X-ray diffraction
Resolution: 1.76 Å
Organism: Homo sapiens
Chains: 3
Atoms: 7,994
Mol. weight: 95.75 kDa
Ligands: GNP, MG, QTM
Released: 26 Aug 2020

Explore 6V9J in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6V9J contains 53 α-helices and 18 β-strands across 3 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: 7 helices, 6 β-strands

Element	Residues	Length	Sheet
β-strand	2-10	9	1
α-helix	16-25	10
β-strand	37-46	10	1
β-strand	49-58	10	1
α-helix	62-67	6
α-helix	69-74	6
β-strand	77-83	7	1
α-helix	87-91	5
α-helix	93-104	12
β-strand	111-116	6	1
α-helix	127-137	11
β-strand	141-143	3	1
α-helix	152-164	13

Chain B: 38 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	566-568	3
α-helix	576-578	3
α-helix	580-581	2
β-strand	586-588	3	2
β-strand	601-604	4	2
α-helix	606-613	8
α-helix	621-630	10
α-helix	631-633	3
α-helix	637-648	12
α-helix	650-655	6
α-helix	657-664	8
α-helix	667-669	3
α-helix	672-677	6
α-helix	678-682	5
α-helix	683-699	17
α-helix	702-706	5
α-helix	708-719	12
α-helix	724-726	3
α-helix	727-742	16
α-helix	757-762	6
α-helix	767	1
α-helix	771-773	3
α-helix	781-797	17
α-helix	801-803	3
α-helix	805-810	6
α-helix	814-817	4
α-helix	819-840	22
α-helix	845-864	20
β-strand	867	1	3
α-helix	868-878	11
α-helix	881-884	4
α-helix	887-892	6
α-helix	895-906	12
α-helix	909-919	11
β-strand	927	1	3
α-helix	931-942	12
β-strand	947-950	4	2
β-strand	953-957	5	2
α-helix	958-974	17
α-helix	977-979	3
α-helix	985-992	8
α-helix	1002-1016	15
α-helix	1018-1019	2
α-helix	1023-1025	3

Chain C: 8 helices, 6 β-strands

Element	Residues	Length	Sheet
β-strand	2-10	9	4
α-helix	18-24	7
β-strand	41-46	6	4
β-strand	49-57	9	4
α-helix	65-67	3
α-helix	68-73	6
β-strand	77-83	7	4
α-helix	87-91	5
α-helix	93-104	12
β-strand	111-117	7	4
α-helix	122-123	2
α-helix	127-137	11
β-strand	141-145	5	4
α-helix	152-164	13

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
GTPase HRas	A	protein	167	Homo sapiens	P01112 (AlphaFold model)
Son of sevenless homolog 1	B	protein	482	Homo sapiens	Q07889 (AlphaFold model)
GTPase HRas	C	protein	167	Homo sapiens	P01112 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>6V9J_1 GTPase HRas (chains A)
GMTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTA
GQEEASAMRDQYMRTGEGFLCVFAINNTKSFEDIHQYREQIKRVKDSDDVPMVLVGNKCD
LAARTVESRQAQDLARSYGIPYIETSAKTRQGVEDAFYTLVREIRQH

Sequence of entity 2 (B), FASTA

>6V9J_2 Son of sevenless homolog 1 (chains B)
GQMRLPSADVYRFAEPDSEENIIFEENMQPKAGIPIIKAGTVIKLIERLTYHMYADPNFV
RTFLTTYRSFCKPQELLSLIIERFEIPEPEPTEADRIAIENGDQPLSAELKRFRKEYIQP
VQLRVLNVCRHWVEHHFYDFERDAYLLQRMEEFIGTVRGKAMKKWVESITKIIQRKKIAR
DNGPGHNITFQSSPPTVEWHISRPGHIETFDLLTLHPIEIARQLTLLESDLYRAVQPSEL
VGSVWTKEDKEINSPNLLKMIRHTTNLTLWFEKCIVETENLEERVAVVSRIIEILQVFQE
LNNFNGVLEVVSAMNSSPVYRLDHTFEQIPSRQKKILEEAHELSEDHYKKYLAKLRSINP
PCVPFFGIYLTNILKTEEGNPEVLKRHGKELINFSKRRKVAEITGEIQQYQNQPYCLRVE
SDIKRFFENLNPMGNSMEKEFTDYLFNKSLEIEPRNPKPLPRFPKKYSYPLKSPGVRPSN
PR

Sequence of entity 3 (C), FASTA

>6V9J_3 GTPase HRas (chains C)
GMTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTA
GQEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHQYREQIKRVKDSDDVPMVLVGNKCD
LAARTVESRQAQDLARSYGIPYIETSAKTRQGVEDAFYTLVREIRQH

Ligands and cofactors

ID	Name	Formula	Copies
GNP	Phosphoaminophosphonic acid-guanylate ester	C10 H17 N6 O13 P3	1
MG	Magnesium ion	Mg	1
QTM	3-(2-aminoethyl)-4-(3-chloro-4-fluorophenoxy)benzene-1-sulfonamide	C14 H14 Cl F N2 O3 S	1

Water and common crystallization additives (FMT, GOL, NA) are not listed.

Primary citation

Discovery of Sulfonamide-Derived Agonists of SOS1-Mediated Nucleotide Exchange on RAS Using Fragment-Based Methods. Sarkar, D., Olejniczak, E.T., Phan, J. et al. J Med Chem (2020) 63:8325-8337. DOI 10.1021/acs.jmedchem.0c00511 · PubMed

Other PDB entries of the same protein (UniProt P01112 (AlphaFold model), which also has an AlphaFold model), best resolution first:

2CE2 1.0 Å, Crystal structure analysis of a fluorescent form of H-ras P21 in complex with GDP
2EVW 1.05 Å, Crystal structure analysis of a fluorescent form of H-Ras p21 in complex with R-caged GTP
24SQ 1.08 Å, Human HRAS WT (GDP-bound) in complex with macrocyclic peptide inhibitor AP6296
8TBG 1.2 Å, Tricomplex of RMC-7977, HRAS WT, and CypA
2CLD 1.22 Å, Crystal structure analysis of a fluorescent form of H-ras P21 in complex with GDP (2)
2CL6 1.24 Å, Crystal structure analysis of a fluorescent form of H-ras P21 in complex with S-caged GTP
2CL7 1.25 Å, Crystal structure analysis of a fluorescent form of H-ras P21 in complex with GTP
5WDQ 1.25 Å, H-Ras mutant L120A bound to GMP-PNP at 100K
1CTQ 1.26 Å, Structure of P21RAS in complex with gppnhp at 100 K
2CLC 1.3 Å, Crystal structure analysis of a fluorescent form of H-ras P21 in complex with GTP (2)
3K8Y 1.3 Å, Allosteric modulation of H-Ras GTPase
3OIW 1.3 Å, H-RasG12V with allosteric switch in the "on" state

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