9CZF: Integrin avb6 headpiece

Crystal structure of integrin avb6 headpiece in complex with compound MORF-627. Determined by X-ray diffraction at 2.53 Å resolution. Released 13 Nov 2024.

Method: X-ray diffraction
Resolution: 2.53 Å
Organisms: Homo sapiens, Mus musculus
Chains: 4
Atoms: 11,874
Mol. weight: 171.37 kDa
Ligands: CA, MAN, MG, A1A6I
Released: 13 Nov 2024

Explore 9CZF in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9CZF contains 50 α-helices and 133 β-strands across 4 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: 14 helices, 58 β-strands

Element	Residues	Length	Sheet
β-strand	3	1	1
β-strand	9-12	4	2
β-strand	22-26	5	3
β-strand	35-40	6	3
β-strand	54	1	4
β-strand	55-60	6	3
β-strand	67-69	3	3
β-strand	79-81	3	5
β-strand	84-85	2	5
β-strand	87-88	2	6
β-strand	94	1	4
β-strand	97-100	4	7
β-strand	105-109	5	7
β-strand	113-114	2	6
β-strand	123	1	6
β-strand	127-131	5	7
β-strand	136-139	4	7
β-strand	160-163	4	8
β-strand	168-173	6	8
α-helix	176-179	4
β-strand	181	1	9
β-strand	182-187	6	8
α-helix	188-193	6
β-strand	208-209	2	8
α-helix	215-217	3
β-strand	222	1	9
β-strand	225-229	5	10
β-strand	238-243	6	10
α-helix	246-249	4
β-strand	252-256	5	10
β-strand	263-268	6	10
β-strand	279-283	5	11
β-strand	292-297	6	11
α-helix	300	1
β-strand	301-303	3	12
α-helix	304	1
β-strand	309-311	3	12
β-strand	314-320	7	11
β-strand	326-332	7	11
β-strand	343-348	6	13
β-strand	357-362	6	13
α-helix	367-369	3
β-strand	372-376	5	13
β-strand	378-379	2	14
β-strand	382-383	2	14
β-strand	389-392	4	13
β-strand	407-412	6	2
β-strand	421-426	6	2
α-helix	427-429	3
β-strand	431-435	5	2
α-helix	436	1
β-strand	437	1	1
α-helix	438-439	2
β-strand	440-450	11	15
β-strand	453-454	2	16
β-strand	461	1	17
β-strand	470	1	17
β-strand	472-483	12	15
β-strand	490-491	2	18
β-strand	493-499	7	19
α-helix	504	1
β-strand	511-513	3	15
β-strand	520-524	5	19
β-strand	527-528	2	18
β-strand	534-542	9	15
α-helix	543-544	2
α-helix	545-547	3
β-strand	555-563	9	19
α-helix	566-568	3
β-strand	577-578	2	15
β-strand	585-590	6	19
β-strand	591-592	2	16

Chain B: 22 helices, 33 β-strands

Element	Residues	Length	Sheet
α-helix	14-20	7
β-strand	25	1	20
β-strand	26	1	21
β-strand	43	1	20
α-helix	45-50	6
β-strand	59	1	21
β-strand	64-69	6	22
α-helix	71-74	4
α-helix	81-83	3
β-strand	87-88	2	23
β-strand	91-96	6	22
β-strand	101-109	9	23
β-strand	116-123	8	24
α-helix	126-128	3
α-helix	129-134	6
α-helix	138-147	10
β-strand	153-160	8	24
α-helix	173-177	5
β-strand	188	1	25
α-helix	189-190	2
β-strand	193-200	8	24
α-helix	203-211	9
β-strand	216	1	25
β-strand	223	1	26
α-helix	225-234	10
α-helix	236-239	4
α-helix	241-242	2
β-strand	246-253	8	24
β-strand	257	1	26
α-helix	260-266	7
β-strand	278	1	27
β-strand	283	1	24
β-strand	284	1	27
α-helix	285-288	4
α-helix	291-294	4
α-helix	295-304	10
β-strand	308-314	7	24
α-helix	315-327	13
β-strand	332-336	5	24
α-helix	343-355	13
β-strand	358-359	2	28
β-strand	360-364	5	22
β-strand	370-377	8	23
β-strand	382-384	3	23
β-strand	388-389	2	28
β-strand	397-405	9	23
β-strand	414-420	7	22
β-strand	427-433	7	22
α-helix	438-441	4
α-helix	448-450	3
β-strand	455-457	3	29
β-strand	462-464	3	29
α-helix	465	1
β-strand	468-469	2	30
β-strand	475-476	2	30

Chain C: 8 helices, 21 β-strands

Element	Residues	Length	Sheet
α-helix	2-3	2
β-strand	4-5	2	31
β-strand	10-13	4	32
β-strand	19-25	7	31
β-strand	33-38	6	32
β-strand	44-49	6	32
β-strand	53-54	2	32
α-helix	55	1
β-strand	62-67	6	31
β-strand	70-75	6	31
α-helix	80-82	3
β-strand	85-90	6	32
α-helix	96	1
β-strand	97-98	2	32
β-strand	102-106	5	32
β-strand	111	1	33
β-strand	114-118	5	34
α-helix	119-121	3
α-helix	122-126	5
β-strand	130-139	10	34
β-strand	140	1	33
β-strand	145-149	5	35
β-strand	154	1	35
β-strand	159-163	5	34
α-helix	164-167	4
β-strand	173-181	9	34
α-helix	183-188	6
β-strand	191-197	7	35
β-strand	205-210	6	35

Chain D: 6 helices, 21 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	36
β-strand	10-12	3	32
β-strand	18-25	8	36
α-helix	29-31	3
β-strand	34-39	6	32
β-strand	45-51	7	32
β-strand	58-60	3	32
α-helix	62-65	4
β-strand	68-73	6	36
β-strand	78-83	6	36
β-strand	92-101	10	32
β-strand	104-108	5	32
β-strand	112-116	5	32
β-strand	122	1	37
β-strand	125-129	5	38
α-helix	130-132	3
β-strand	140-150	11	38
β-strand	151	1	37
β-strand	156-159	4	39
β-strand	168-170	3	38
α-helix	171-173	3
β-strand	174-176	3	38
β-strand	179-189	11	38
α-helix	190-192	3
β-strand	199-204	6	39
α-helix	205-207	3
β-strand	209-214	6	39

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Integrin alpha-V heavy chain	A	protein	605	Homo sapiens	P06756 (AlphaFold model)
Integrin beta-6	B	protein	481	Homo sapiens	P18564 (AlphaFold model)
17E6 Fab light chain	C	protein	214	Mus musculus
17E6 Fab heavy chain	D	protein	218	Mus musculus

Sequence of entity 1 (A), FASTA

>9CZF_1 Integrin alpha-V heavy chain (chains A)
FNLDVDSPAEYSGPEGSYFGFAVDFFVPSASSRMFLLVGAPKANTTQPGIVEGGQVLKCD
WSSTRRCQPIEFDATGNRDYAKDDPLEFKSHQWFGASVRSKQDKILACAPLYHWRTEMKQ
EREPVGTCFLQDGTKTVEYAPCRSQDIDADGQGFCQGGFSIDFTKADRVLLGGPGSFYWQ
GQLISDQVAEIVSKYDPNVYSIKYNNQLATRTAQAIFDDSYLGYSVAVGDFNGDGIDDFV
SGVPRAARTLGMVYIYDGKNMSSLYNFTGEQMAAYFGFSVAATDINGDDYADVFIGAPLF
MDRGSDGKLQEVGQVSVSLQRASGDFQTTKLNGFEVFARFGSAIAPLGDLDQDGFNDIAI
AAPYGGEDKKGIVYIFNGRSTGLNAVPSQILEGQWAARSCPPSFGYSMKGATDIDKNGYP
DLIVGAFGVDRAILYRARPVITVNAGLEVYPSILNQDNKTCSLPGTALKVSCFNVRFCLK
ADGKGVLPRKLNFQVELLLDKLKQKGAIRRALFLYSRSPSHSKNMTISRGGLMQCEELIA
YLRDESEFRDKLTPITIFMEYRLDYRTAADTTGLQPILNQFTPANISRQAHILLDGGSLE
VLFQG

Sequence of entity 2 (B), FASTA

>9CZF_2 Integrin beta-6 (chains B)
GCALGGAETCEDCLLIGPQCAWCAQENFTHPSGVGERCDTPANLLAKGCQLNFIENPVSQ
VEILKNKPLSVGRQKNSSDIVQIAPQSLILKLRPGGAQTLQVHVRQTEDYPVDLYYLMDL
SASMDDDLNTIKELGSRLSKEMSKLTSNFRLGFGSFVEKPVSPFVKTTPEEIANPCSSIP
YFCLPTFGFKHILPLTNDAERFNEIVKNQKISANIDTPEGGFDAIMQAAVCKEKIGWRND
SLHLLVFVSDADSHFGMDSKLAGIVCPNDGLCHLDSKNEYSMSTVLEYPTIGQLIDKLVQ
NNVLLIFAVTQEQVHLYENYAKLIPGATVGLLQKDSGNILQLIISAYEELRSEVELEVLG
DTEGLNLSFTAICNNGTLFQHQKKCSHMKVGDTASFSVTVNIPHCERRSRHIIIKPVGLG
DALELLVSPECNCDCQKEVEVNSSKCHHGNGSFQCGVCACHPGHMGPRCESGHSLEVLFQ
G

Sequence of entity 3 (C), FASTA

>9CZF_3 17E6 Fab light chain (chains C)
DIQMTQTTSSLSASLGDRVIISCRASQDISNYLSWYQQKPDGTVKLLIFYTSKLHSGVPS
RFSGSGSGTDYSLTISNLDQEDIATYFCQQGNTFPYTFGGGTKVEMRRADAAPTVSIFPP
SSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSFSSTLT
LTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

Sequence of entity 4 (D), FASTA

>9CZF_4 17E6 Fab heavy chain (chains D)
QVQLQQSGAELAEPGASVKMSCKASGYTFSSFWMHWVKQRPGQGLEWIGYINPNSGYTEC
NEIFRDKATMTADTSSSTAYMQLSGLTSEDSAVYYCASFLGRGAMDYWGQGTSVTVSSAK
TTAPSVYPLAPVCGDTTGSSVTLGCLVKGYFPEPVTLTWNSGSLSAGVHTFPAVLQSSLY
TLSSSVTVVASTWPSQSITCNVAHPASSTKVDKKIEPR

Ligands and cofactors

ID	Name	Formula	Copies
CA	Calcium ion	Ca	6
MAN	alpha-D-mannopyranose	C6 H12 O6	2
MG	Magnesium ion	Mg	1
A1A6I	(2S)-{5-fluoro-2-[(6S)-5-oxaspiro[2.5]octan-6-yl]phenyl}{(3R)-3-[4-(5,6,7,8-tet…	C31 H40 F N3 O4	1
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	1

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

Primary citation

The Discovery of MORF-627, a Highly Selective Conformationally-Biased Zwitterionic Integrin alpha v beta 6 Inhibitor for Fibrosis. Harrison, B.A., Dowling, J.E., Bursavich, M.G. et al. J Med Chem (2024) 67:18656-18681. DOI 10.1021/acs.jmedchem.4c01851 · PubMed

Other PDB entries of the same protein (UniProt P06756 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9CZD 2.23 Å, Crystal structure of integrin avb6 headpiece in complex with compound 30
5FFG 2.25 Å, Crystal structure of integrin alpha V beta 6 head
8W30 2.45 Å, Crystal structure of alpha-V beta-1 integrin headpiece in complex with TR01225179
9CZA 2.49 Å, Crystal structure of integrin avb6 headpiece in complex with compound 18
4UM9 2.5 Å, Crystal structure of alpha V beta 6 with peptide
9CZ7 2.57 Å, Crystal structure of integrin avb6 headpiece in complex with compound 12
6OM1 2.66 Å, Crystal structure of an atypical integrin
8VS6 2.73 Å, L-TGF-b3/avb8
6OM2 2.77 Å, Crystal structure of atypical integrin alphaV beta8 with proTGF-beta1 ligand peptide
9IUJ 2.78 Å, Integrin alpha-v beta-3 in complex with rhodostomin
9LT3 2.79 Å, Integrin alpha-v beta-3 in complex with Trimucrin
8XEL 2.8 Å, Cryo-EM structure of integrin ITGAV/ITGB3 complex, conformation 3

Browse structure collections

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