9CZA: Integrin avb6 headpiece

Crystal structure of integrin avb6 headpiece in complex with compound 18. Determined by X-ray diffraction at 2.49 Å resolution. Released 13 Nov 2024.

Method: X-ray diffraction
Resolution: 2.49 Å
Organisms: Homo sapiens, Mus musculus
Chains: 4
Atoms: 11,891
Mol. weight: 171.78 kDa
Ligands: CA, MAN, MG, A1A6B
Released: 13 Nov 2024

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

Secondary structure: helices and β-sheets

9CZA contains 47 α-helices and 128 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: 11 helices, 54 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	55-59	5	3
β-strand	67-69	3	3
α-helix	77-78	2
β-strand	79-81	3	4
β-strand	84-85	2	4
β-strand	87-88	2	5
β-strand	97-101	5	6
β-strand	104-109	6	6
β-strand	113-114	2	5
β-strand	123	1	5
β-strand	127-131	5	6
β-strand	136-139	4	6
β-strand	160-163	4	7
β-strand	168-173	6	7
α-helix	176-179	4
β-strand	181	1	8
β-strand	182-187	6	7
α-helix	188-193	6
β-strand	208-209	2	7
α-helix	215-217	3
β-strand	222	1	8
β-strand	225-229	5	9
β-strand	238-243	6	9
α-helix	246-249	4
β-strand	252-256	5	9
β-strand	263-268	6	9
β-strand	279-283	5	10
β-strand	292-297	6	10
β-strand	301-303	3	11
β-strand	309-311	3	11
β-strand	314-320	7	10
β-strand	326-332	7	10
β-strand	343-348	6	12
β-strand	357-362	6	12
α-helix	367-369	3
β-strand	372-377	6	12
β-strand	378-379	2	13
β-strand	382-383	2	13
β-strand	389-392	4	12
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	14
β-strand	453-454	2	15
β-strand	461	1	16
β-strand	470	1	16
β-strand	472-483	12	14
β-strand	490-499	10	17
β-strand	511-513	3	14
β-strand	520-528	9	17
β-strand	534-542	9	14
α-helix	545-547	3
β-strand	555-563	9	17
α-helix	566-568	3
β-strand	577-578	2	14
β-strand	585-590	6	17
β-strand	591-592	2	15

Chain B: 21 helices, 31 β-strands

Element	Residues	Length	Sheet
α-helix	14-20	7
β-strand	25	1	18
β-strand	43	1	18
α-helix	45-50	6
α-helix	55-58	4
β-strand	64-69	6	19
α-helix	71-74	4
α-helix	81-83	3
β-strand	87-88	2	20
β-strand	91-95	5	19
α-helix	96-97	2
β-strand	101-109	9	20
β-strand	116-123	8	21
α-helix	126-128	3
α-helix	129-134	6
α-helix	138-147	10
β-strand	153-160	8	21
α-helix	173-177	5
α-helix	188-190	3
β-strand	193-200	8	21
α-helix	203-212	10
β-strand	223	1	22
α-helix	225-234	10
α-helix	236-239	4
β-strand	246-253	8	21
β-strand	257	1	22
α-helix	260-266	7
β-strand	278	1	23
β-strand	283	1	21
β-strand	284	1	23
α-helix	291-294	4
α-helix	295-304	10
β-strand	308-313	6	21
α-helix	315-327	13
β-strand	332-335	4	21
α-helix	343-355	13
β-strand	358-359	2	24
β-strand	360-364	5	19
β-strand	370-377	8	20
β-strand	382-384	3	20
β-strand	388-389	2	24
β-strand	394	1	25
β-strand	396	1	25
β-strand	397-405	9	20
β-strand	414-420	7	19
β-strand	427-431	5	19
α-helix	438-441	4
β-strand	455-457	3	26
β-strand	462-464	3	26
α-helix	465	1
β-strand	468-469	2	27
β-strand	475-476	2	27

Chain C: 8 helices, 21 β-strands

Element	Residues	Length	Sheet
β-strand	4-5	2	28
β-strand	10-13	4	29
β-strand	19-25	7	28
β-strand	33-38	6	29
β-strand	44-49	6	29
β-strand	53-54	2	29
α-helix	55	1
β-strand	62-67	6	28
β-strand	70-75	6	28
α-helix	80-82	3
β-strand	85-90	6	29
α-helix	96	1
β-strand	97-98	2	29
β-strand	102-106	5	29
β-strand	111	1	30
α-helix	112-113	2
β-strand	114-118	5	31
α-helix	119-121	3
α-helix	122-125	4
β-strand	130-139	10	31
β-strand	140	1	30
β-strand	145-149	5	32
β-strand	154	1	32
β-strand	159-163	5	31
α-helix	164-167	4
β-strand	173-181	9	31
α-helix	183-186	4
β-strand	191-198	8	32
β-strand	201-210	10	32

Chain D: 7 helices, 22 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	33
β-strand	10-12	3	34
β-strand	17-25	9	33
α-helix	29-31	3
β-strand	34-39	6	34
β-strand	45-51	7	34
β-strand	58-60	3	34
β-strand	68-73	6	33
β-strand	78-84	7	33
α-helix	88-90	3
β-strand	92-101	10	34
β-strand	104-108	5	34
β-strand	112-116	5	34
β-strand	122	1	35
α-helix	123-124	2
β-strand	125-129	5	36
β-strand	140-150	11	36
β-strand	151	1	35
β-strand	156-159	4	37
α-helix	160-162	3
β-strand	164	1	37
β-strand	168-170	3	36
α-helix	171-173	3
β-strand	174-176	3	36
β-strand	179-189	11	36
α-helix	190-192	3
β-strand	199-204	6	37
α-helix	205-207	3
β-strand	209-214	6	37

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

>9CZA_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

>9CZA_2 Integrin beta-6 (chains B)
GCALGGAETCEDCLLIGPQCAWCAQENFTHPSGVGERCDTPANLLAKGCQLNFIENPVSQ
VEILKNKPLSVGRQKNSSDIVQIAPQSLILKLRPGGAQTLQVHVRQTEDYPVDLYYLMDL
SASMDDDLNTIKELGSRLSKEMSKLTSNFRLGFGSFVEKPVSPFVKTTPEEIANPCSSIP
YFCLPTFGFKHILPLTNDAERFNEIVKNQKISANIDTPEGGFDAIMQAAVCKEKIGWRND
SLHLLVFVSDADSHFGMDSKLAGIVCPNDGLCHLDSKNEYSMSTVLEYPTIGQLIDKLVQ
NNVLLIFAVTQEQVHLYENYAKLIPGATVGLLQKDSGNILQLIISAYEELRSEVELEVLG
DTEGLNLSFTAICNNGTLFQHQKKCSHMKVGDTASFSVTVNIPHCERRSRHIIIKPVGLG
DALELLVSPECNCDCQKEVEVNSSKCHHGNGSFQCGVCACHPGHMGPRCESGHSLEVLFQ
G

Sequence of entity 3 (C), FASTA

>9CZA_3 17E6 Fab light chain (chains C)
DIQMTQTTSSLSASLGDRVIISCRASQDISNYLSWYQQKPDGTVKLLIFYTSKLHSGVPS
RFSGSGSGTDYSLTISNLDQEDIATYFCQQGNTFPYTFGGGTKVEMRRADAAPTVSIFPP
SSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSFSSTLT
LTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

Sequence of entity 4 (D), FASTA

>9CZA_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	1
MG	Magnesium ion	Mg	1
A1A6B	(2S)-(2-cyclopropylphenyl){(3R)-3-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)…	C27 H35 N3 O3	1
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	2

Water and common crystallization additives (GOL, ACT) 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
4UM9 2.5 Å, Crystal structure of alpha V beta 6 with peptide
9CZF 2.53 Å, Crystal structure of integrin avb6 headpiece in complex with compound MORF-627
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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