7TPP: Human prothrombin:prothrombinase

Cryo-em structure of human prothrombin:prothrombinase at 4.1 Angstrom resolution. Determined by electron microscopy at 4.1 Å resolution. Released 4 May 2022.

Method: Electron microscopy
Resolution: 4.1 Å
Organism: Homo sapiens
Chains: 5
Atoms: 18,513
Mol. weight: 266.21 kDa
Released: 4 May 2022

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

Secondary structure: helices and β-sheets

7TPP contains 40 α-helices and 172 β-strands across 5 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: 6 helices, 4 β-strands

Element	Residues	Length	Sheet
α-helix	4-10	7
α-helix	26-31	6
α-helix	35-42	8
α-helix	72-73	2
β-strand	77	1	11
β-strand	83	1	11
α-helix	91-95	5
β-strand	115	1	12
α-helix	124-125	2
β-strand	126	1	12

Chain B: 6 helices, 18 β-strands

Element	Residues	Length	Sheet
α-helix	199	1
β-strand	200	1	66
α-helix	201-202	2
β-strand	211-213	3	67
β-strand	219-222	4	67
β-strand	225	1	68
β-strand	231	1	68
β-strand	232-233	2	69
β-strand	245-247	3	67
β-strand	265-268	4	70
β-strand	284-285	2	69
β-strand	286-288	3	70
α-helix	306-309	4
β-strand	320	1	71
β-strand	323	1	66
β-strand	338	1	66
β-strand	341	1	71
α-helix	347-349	3
α-helix	357-358	2
β-strand	363	1	72
β-strand	382-385	4	73
β-strand	392-396	5	73
β-strand	412	1	72
α-helix	419-424	6

Chain C: 12 helices, 60 β-strands

Element	Residues	Length	Sheet
β-strand	3	1	13
β-strand	7-13	7	14
β-strand	35-40	6	14
β-strand	41	1	15
β-strand	48	1	15
β-strand	62-64	3	16
β-strand	69-70	2	13
β-strand	73-76	4	14
β-strand	82	1	17
β-strand	85	1	18
α-helix	93-95	3
α-helix	106-111	6
β-strand	114	1	17
β-strand	118-121	4	14
β-strand	124-125	2	13
α-helix	128-130	3
β-strand	139-144	6	16
β-strand	145	1	18
α-helix	152-155	4
β-strand	160-165	6	16
β-strand	170	1	19
β-strand	176	1	19
α-helix	215-216	2
β-strand	217-218	2	20
β-strand	221	1	21
β-strand	224-229	6	22
β-strand	238	1	23
β-strand	241-242	2	24
β-strand	243	1	20
β-strand	250	1	25
β-strand	253	1	25
β-strand	257-258	2	24
β-strand	261	1	23
β-strand	266-271	6	22
β-strand	276-280	5	20
β-strand	294-298	5	20
β-strand	300	1	21
β-strand	325-328	4	26
β-strand	329	1	27
α-helix	345-347	3
α-helix	348-352	5
α-helix	355-357	3
β-strand	367	1	27
β-strand	371	1	26
β-strand	379	1	26
β-strand	396	1	28
β-strand	405-409	5	26
β-strand	415	1	29
β-strand	447	1	29
β-strand	452-455	4	26
α-helix	461-463	3
β-strand	473-475	3	28
β-strand	478	1	30
α-helix	485-488	4
β-strand	492	1	30
β-strand	495-497	3	28
β-strand	515-516	2	31
β-strand	519	1	32
β-strand	521-523	3	33
α-helix	530-533	4
α-helix	550-556	7
β-strand	558-560	3	33
β-strand	561	1	34
β-strand	564	1	34
β-strand	581-584	4	31
β-strand	585	1	32
β-strand	588	1	33
β-strand	594-596	3	35
β-strand	613-615	3	35
β-strand	621-623	3	31
β-strand	631	1	36
β-strand	653	1	36

Chain D: 4 helices, 65 β-strands

Element	Residues	Length	Sheet
β-strand	1557-1559	3	37
β-strand	1563-1564	2	38
α-helix	1567-1570	4
β-strand	1586-1587	2	38
β-strand	1591-1593	3	37
β-strand	1595	1	39
β-strand	1603	1	39
β-strand	1632-1633	2	40
β-strand	1634	1	41
β-strand	1643-1644	2	42
α-helix	1672-1673	2
β-strand	1674	1	41
β-strand	1677-1678	2	40
β-strand	1697-1701	5	43
β-strand	1702-1703	2	42
β-strand	1719-1723	5	43
β-strand	1731	1	44
β-strand	1734	1	44
β-strand	1741-1744	4	45
β-strand	1745	1	46
β-strand	1748	1	47
β-strand	1777	1	47
β-strand	1780	1	46
β-strand	1783	1	46
β-strand	1791-1793	3	48
β-strand	1799-1803	5	45
β-strand	1813-1814	2	49
β-strand	1815-1816	2	50
β-strand	1823	1	51
β-strand	1829	1	51
β-strand	1834-1835	2	49
β-strand	1841-1845	5	45
β-strand	1854	1	52
β-strand	1856-1857	2	50
β-strand	1872	1	52
β-strand	1873-1875	3	48
β-strand	1887	1	53
β-strand	1896-1897	2	54
β-strand	1935-1950	16	54
β-strand	1962	1	55
β-strand	1966-1968	3	54
β-strand	1969	1	56
β-strand	1977	1	56
β-strand	2000-2016	17	54
β-strand	2020	1	55
β-strand	2040	1	57
β-strand	2061	1	58
β-strand	2067	1	58
β-strand	2084	1	59
β-strand	2097-2098	2	60
β-strand	2107-2109	3	61
β-strand	2114	1	62
β-strand	2119	1	62
β-strand	2121	1	63
β-strand	2124-2129	6	64
β-strand	2137-2138	2	64
α-helix	2139	1
β-strand	2140	1	65
α-helix	2141	1
β-strand	2147	1	65
β-strand	2150-2151	2	64
β-strand	2159	1	53
β-strand	2172-2173	2	60
β-strand	2174-2177	4	64
β-strand	2181	1	63
β-strand	2183	1	63
β-strand	2186	1	59
β-strand	2189-2191	3	61
β-strand	2192	1	57

Chain E: 12 helices, 25 β-strands

Element	Residues	Length	Sheet
α-helix	40-43	4
α-helix	84-88	5
β-strand	91	1	1
α-helix	105-107	3
β-strand	127	1	2
β-strand	135	1	2
α-helix	151-152	2
α-helix	172-175	4
β-strand	220	1	3
β-strand	230	1	3
β-strand	242	1	3
α-helix	283-286	4
β-strand	336-339	4	4
β-strand	346-349	4	4
β-strand	350	1	5
β-strand	359-361	3	5
α-helix	368-370	3
β-strand	380-383	4	4
β-strand	398	1	4
β-strand	401-405	5	5
β-strand	411	1	6
β-strand	417	1	6
β-strand	420-425	6	5
β-strand	458	1	7
β-strand	462	1	8
α-helix	464-466	3
β-strand	469	1	1
β-strand	483	1	7
α-helix	491-493	3
β-strand	505-506	2	9
α-helix	510-512	3
β-strand	523	1	8
β-strand	528-533	6	10
β-strand	538-544	7	10
β-strand	560-561	2	9
α-helix	568-571	4
α-helix	575-577	3

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Prothrombin	E	protein	579	Homo sapiens	P00734 (AlphaFold model)
Factor X light chain	A	protein	139	Homo sapiens	P00742 (AlphaFold model)
Coagulation factor Va	C	protein	709	Homo sapiens	P12259 (AlphaFold model)
Coagulation factor Va	D	protein	651	Homo sapiens	P12259 (AlphaFold model)
Activated factor Xa heavy chain	B	protein	254	Homo sapiens	P00742 (AlphaFold model)

Sequence of entity 1 (E), FASTA

>7TPP_1 Prothrombin (chains E)
ANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAAC
LEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSS
TTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQG
RLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDF
GYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFE
KKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLT
AAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDI
ALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVL
QVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDAGGPFVMKSPFNNRWY
QMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE

Sequence of entity 2 (A), FASTA

>7TPP_2 Factor X light chain (chains A)
ANSFLEEMKKGHLERECMEETCSYEEAREVFEDSDKTNEFWNKYKDGDQCETSPCQNQGK
CKDGLGEYTCTCLEGFEGKNCELFTRKLCSLDNGDCDQFCHEEQNSVVCSCARGYTLADN
GKACIPTGPYPCGKQTLER

Sequence of entity 3 (C), FASTA

>7TPP_3 Coagulation factor Va (chains C)
AQLRQFYVAAQGISWSYRPEPTNSSLNLSVTSFKKIVYREYEPYFKKEKPQSTISGLLGP
TLYAEVGDIIKVHFKNKADKPLSIHPQGIRYSKLSEGASYLDHTFPAEKMDDAVAPGREY
TYEWSISEDSGPTHDDPPCLTHIYYSHENLIEDFNSGLIGPLLICKKGTLTEGGTQKTFD
KQIVLLFAVFDESKSWSQSSSLMYTVNGYVNGTMPDITVCAHDHISWHLLGMSSGPELFS
IHFNGQVLEQNHHKVSAITLVSATSTTANMTVGPEGKWIISSLTPKHLQAGMQAYIDIKN
CPKKTRNLKKITREQRRHMKRWEYFIAAEEVIWDYAPVIPANMDKKYRSQHLDNFSNQIG
KHYKKVMYTQYEDESFTKHTVNPNMKEDGILGPIIRAQVRDTLKIVFKNMASRPYSIYPH
GVTFSPYEDEVNSSFTSGRNNTMIRAVQPGETYTYKWNILEFDEPTENDAQCLTRPYYSD
VDIMRDIASGLIGLLLICKSRSLDRRGIQRAADIEQQAVFAVFDENKSWYLEDNINKFCE
NPDEVKRDDPKFYESNIMSTINGYVPESITTLGFCFDDTVQWHFCSVGTQNEILTIHFTG
HSFIYGKRHEDTLTLFPMRGESVTVTMDNVGTWMLTSMNSSPRSKKLRLKFRDVKCIPDD
DEDSYEIFEPPESTVMATRKMHDRLEPEDEESDADYDYQNRLAAALGIR

Sequence of entity 4 (D), FASTA

>7TPP_4 Coagulation factor Va (chains D)
SNNGNRRNYYIAAEEISWDYSEFVQRETDIEDSDDIPEDTTYKKVVFRKYLDSTFTKRDP
RGEYEEHLGILGPIIRAEVDDVIQVRFKNLASRPYSLHAHGLSYEKSSEGKTYEDDSPEW
FKEDNAVQPNSSYTYVWHATERSGPESPGSACRAWAYYSAVNPEKDIHSGLIGPLLICQK
GILHKDSNMPMDMREFVLLFMTFDEKKSWYYEKKSRSSWRLTSSEMKKSHEFHAINGMIY
SLPGLKMYEQEWVRLHLLNIGGSQDIHVVHFHGQTLLENGNKQHQLGVWPLLPGSFKTLE
MKASKPGWWLLNTEVGENQRAGMQTPFLIMDRDCRMPMGLSTGIISDSQIKASEFLGYWE
PRLARLNNGGSYNAWSVEKLAAEFASKPWIQVDMQKEVIITGIQTQGAKHYLKSCYTTEF
YVAYSSNQINWQIFKGNSTRNVMYFNGNSDASTIKENQFDPPIVARYIRISPTRAYNRPT
LRLELQGCEVNGCSTPLGMENGKIENKQITASSFKKSWWGDYWEPFRARLNAQGRVNAWQ
AKANNNKQWLEIDLLKIKKITAIITQGCKSLSSEMYVKSYTIHYSEQGVEWKPYRLKSSM
VDKIFEGNTNTKGHVKNFFNPPIISRFIRVIPKTWNQSIALRLELFGCDIY

Sequence of entity 5 (B), FASTA

>7TPP_5 Activated factor Xa heavy chain (chains B)
IVGGQECKDGECPWQALLINEENEGFCGGTILSEFYILTAAHCLYQAKRFKVRVGDRNTE
QEEGGEAVHEVEVVIKHNRFTKETYDFDIAVLRLKTPITFRMNVAPACLPERDWAESTLM
TQKTGIVSGFGRTHEKGRQSTRLKMLEVPYVDRNSCKLSSSFIITQNMFCAGYDTKQEDA
CQGDAGGPHVTRFKDTYFVTGIVSWGEGCARKGKYGIYTKVTAFLKWIDRSMKTRGLPKA
KSHAPEVITSSPLK

Primary citation

Cryo-EM structure of the prothrombin-prothrombinase complex. Ruben, E.A., Summers, B., Rau, M.J. et al. Blood (2022) 139:3463-3473. DOI 10.1182/blood.2022015807 · PubMed

Other PDB entries of the same protein (UniProt P00734 (AlphaFold model), which also has an AlphaFold model), best resolution first:

5AFY 1.12 Å, Thrombin in complex with 3-chloro-benzamide
4UD9 1.12 Å, Thrombin in complex with 5-chlorothiophene-2-carboxamide
4UE7 1.13 Å, Thrombin in complex with 1-amidinopiperidine
4UDW 1.16 Å, Thrombin in complex with 1-(2R)-2-amino-3-phenyl-propanoyl-N-(2,…
4UEH 1.16 Å, Thrombin in complex with benzamidine
5AF9 1.18 Å, Thrombin in complex with 4-Methoxy-N-(2-pyridinyl)benzamide
3RM2 1.23 Å, Human Thrombin in complex with MI003
5AHG 1.24 Å, Thrombin in complex with ((4-chlorophenyl)sulfamoyl))diemethylamine
2BVR 1.25 Å, Human thrombin complexed with fragment-based small molecules occupying the S1 pocket
3VXE 1.25 Å, Human alpha-thrombin-Bivalirudin complex at PD5.0
2UUF 1.26 Å, Thrombin-hirugen binary complex at 1.26A resolution
3SI4 1.27 Å, Human Thrombin In Complex With UBTHR104

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