CODSWALLOP

Serine protease 1

Bos taurus · seed P00760 · 246 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026

CATH and SCOP identifiers come from the RCSB's own structure annotations, which the Domains panel already reads, so these are looked up rather than guessed at.

1,915Entries 2,000Entities 414Constructs 32Organisms 1,380Ligand-bound
0.75 ÅBest res.
1.85 ÅMedian res.

Every figure here is counted over the whole family rather than quoted from one entry.

The reference structure

1NTP, the structure every other member of this family is superposed onto. Rendered by the RCSB and embedded here: the live app shows an interactive viewport, which a document that fetches nothing cannot.

Rendered structure of 1NTP
1NTP at the RCSB · open it in the 3D viewer

Which residues anyone has ever seen

How many of this family's constructs contain each residue of the seed. A trough is a stretch nobody has put in a construct, which is a construct-design answer rather than a disorder one.

11232461929 constructs

Constructs, most-used first

414 distinct constructs across 1,915 entries. 1,825 polymer entities differ from the UniProt canonical sequence in some way, 78 carry a recognised expression tag and 3 carry a fusion partner.

"Differs from canonical" is not the same as "engineered". The canonical sequence is the full gene product, so a secreted protein whose structures all start after its signal peptide counts every one of them as different: lysozyme's most-used construct, residues 19–147 on 1,239 entities, is simply the mature protein. Read the construct column below for what was actually done, rather than this count.

EntitiesLengthBest (Å)Best entryWhat was made
486 223 0.75 4I8H residues 24-246
102 254 1.36 5PAG residues 213-466
57 131 1.00 5R43 residues 16-146
55 97 1.00 5R43 residues 149-245
46 254 1.55 4Y6D residues 235-488
37 244 1.55 5TKS His6; residues 388-625; N491G, T493G
34 245 1.70 1T8O matches the canonical sequence
30 253 1.40 6XVD residues 179-431; C299A, N322Q
28 234 1.50 2PR3 residues 235-468
28 238 0.92 7MBO residues 388-625; C500S
25 246 0.91 4XOJ matches the canonical sequence
23 229 1.50 1BTY residues 18-246
23 238 1.25 4CRG residues 388-625; S452A, K455A, T493A +1 more
22 223 1.25 1S83 residues 9-231
19 246 1.18 5YC6 residues 179-424; C299A, N322Q
18 226 1.13 7H66 residues 22-247; C28S, F135K
17 224 0.80 1PQ7 residues 25-248
17 245 1.45 5Z1C residues 179-423; C299A, N322Q
17 245 1.65 4MPU residues 31-275; R51H, D52G, R53P +1 more
17 259 1.32 2UUJ residues 364-622
16 223 1.00 4K8Y residues 31-253; H197Q
16 232 1.17 5NAT residues 26-253
16 235 1.90 1G2L residues 235-469
15 233 1.62 2P3U residues 235-467
14 243 1.15 1UTN residues 4-246

Showing the 25 most-used of 414.

Positions people deliberately mutate

Columns where the wild-type residue still dominates but a real minority carries something else, which is a different question from "what varies across species".

G31K 68% T34E 68% S125P 67% S98D 66% V81E 66% Q138L 66% S237D 66% V35W 65% S181D 65% D76H 65% S93V 64% Q178K 64% S55E 64% S169E 64% V95I 64% D168N 64% N102E 63% G68R 63% T29E 63% A116P 63% A174S 62% S89E 62% T130S 62% R122T 62% A163V 62% S91E 62% A32P 62% S153L 62% Y28E 61% N33G 61%

What it assembles into

Oligomeric stateChainsEntriesShare
monomeric1 959 50.1%
dimeric2 620 32.4%
trimeric3 159 8.3%
tetrameric4 97 5.1%
pentameric5 28 1.5%
hexameric6 27 1.4%
octameric8 17 0.9%
dodecameric12 5 0.3%

1,182 entries have the depositor's assembly corroborated by PISA, 670 carry the depositor's word alone and 63 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 93 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 1AB9, 1BML, 1BQY, 1CBW, 1DLK, 1FIZ, 1GGD, 1GHB, 1GMH, 1K2I, 1KLI, 1L4D, 1L4Z, 1MTN, 1OPH, 1P2J, 1P2M, 1P2N, 1P2O, 1P2Q.

Domain architecture

Every source's own domains on the seed axis, one row each. They are not merged: Pfam, CATH, SCOP and InterPro disagree about boundaries, and a merged track would state a consensus none of them gave.

CATHTrypsin-like serine proteaSCOP2BTrypsin-like serine proteaTrypsin-like serine proteaTrypsin-like serine proteaTrypsin-like serine proteaTrypsin-like serine proteaTrypsin-like serine proteaTrypsin-like serine proteaTrypsin-like serine proteaTrypsin-like serine proteaTrypsin-like serine proteaTrypsin-like serine proteaTrypsin-like serine protea1123246
DomainSourceSpan (seed)Chains
Trypsin-like serine proteasesCATH 2.40.10.10 126–232 4,662
Trypsin-like serine proteasesSCOP2B 8042128 23–246 28
Trypsin-like serine proteasesSCOP2B 8037496 24–246 531
Trypsin-like serine proteasesSCOP2B 8035341 24–246 129
Trypsin-like serine proteasesSCOP2B 8044201 24–246 105
Trypsin-like serine proteasesSCOP2B 8042234 24–246 36
Trypsin-like serine proteasesSCOP2B 8036522 24–246 33
Trypsin-like serine proteasesSCOP2B 8042143 24–246 23
Trypsin-like serine proteasesSCOP2B 8035635 24–246 22
Trypsin-like serine proteasesSCOP2B 8041386 24–244 20
Trypsin-like serine proteasesSCOP2B 8033466 26–246 36
Trypsin-like serine proteasesSCOP2B 8042267 26–246 22

What binds it

BEN BEN184 entries NAG NAG120 entries FUC FUC35 entries BGC BGC22 entries 0GJ 0GJ16 entries 0G6 0G615 entries GBS GBS14 entries MRZ MRZ12 entries ANH ANH11 entries PBZ PBZ10 entries GSH GSH10 entries ABN ABN9 entries
ComponentClassNameEntriesBest (Å)
CAion Calcium Ion 972 0.75
SO4ion Sulfate Ion 712 0.75
GOLcryoprotectant Glycerol 322 0.75
BENligand Benzamidine 184 0.75
CLion Chloride Ion 144 1.15
EDOcryoprotectant 1,2-Ethanediol 122 0.91
NAGcofactor 2-Acetamido-2-Deoxy-Beta-D-Glucopyranose 120 0.92
NAion Sodium Ion 106 0.91
DMScryoprotectant Dimethyl Sulfoxide 103 0.95
ZNion Zinc Ion 63 1.13
ACTcryoprotectant Acetate Ion 60 0.93
MGion Magnesium Ion 54 1.25
CITbuffer Citric Acid 40 1.00
FUCcofactor Alpha-L-Fucopyranose 35 1.25
PO4ion Phosphate Ion 25 1.16
PEGcryoprotectant Di(Hydroxyethyl)ether 25 1.18
BGCligand Beta-D-Glucopyranose 22 1.72
PGEcryoprotectant Triethylene Glycol 21 1.18
MESbuffer 2-(N-Morpholino)-Ethanesulfonic Acid 20 0.97
PG4cryoprotectant Tetraethylene Glycol 20 1.18

How it crystallises

Parsed from the free text 1,578 depositors typed into _exptl_crystal_grow.pdbx_details, out of 1,671 entries that recorded anything at all. Median pH 7.0 (range 2.0 to 10.5).

Precipitants

PEG × Ammonium sulfate × Calcium chloride × Sodium chloride × Sodium citrate × Lithium sulfate × Magnesium chloride × Isopropanol × MPD × Sodium malonate × Sodium formate × Dioxane × Tacsimate × PEG (unspecified) ×

Buffers

Tris × HEPES × MES × Citrate × Sodium acetate × Sodium cacodylate × Imidazole × Phosphate × Bis-Tris × Succinate × CHES × Bis-Tris propane × ADA × CAPS ×

Which entries to trust

1,913 entries carry a wwPDB validation report: 1,069 clean, 532 worth a check and 312 with something to explain. Median clashscore 5.1, median RSRZ outliers 2.24%, median R-free minus R-work 0.035. 1,722 have released structure factors.

Across species

OrganismEntriesBest (Å)Ligand-boundSeed covered
Homo sapiens1,019 0.92 792 100%
Bos taurus711 0.75 515 100%
Sus scrofa52 1.18 20 94%
Rattus norvegicus30 1.46 6 100%
Mus musculus19 1.25 9 91%
Fusarium oxysporum17 0.80 4 85%
Salmo salar11 1.00 7 100%
Rattus rattus11 1.59 7 94%
Streptomyces griseus7 1.05 3 88%
Saccharopolyspora erythraea5 0.78 0 89%
Oncorhynchus keta4 1.55 4 90%
Daboia siamensis4 1.80 4 91%

Seed sequence

246 residues, numbered every ten. Every identity figure in this document is measured against this sequence.

active or binding site modified residue or glycosylation disulphide cysteine transmembrane or signal the 15 most-substituted positions

1MKTFIFLALL GAAVAFPVDD DDKIVGGYTC GANTVPYQVS LNSGYHFCGG SLINSQWVVS
61AAHCYKSGIQ VRLGEDNINV VEGNEQFISA SKSIVHPSYN SNTLNNDIML IKLKSAASLN
121SRVASISLPT SCASAGTQCL ISGWGNTKSS GTSYPDVLKC LKAPILSDSS CKSAYPGQIT
181SNMFCAGYLE GGKDSCQGDS GGPVVCSGKL QGIVSWGSGC AQKNKPGVYT KVCNYVSWIK
241QTIASN

Sites are UniProt's curated features where the seed is a UniProt accession; the substituted positions are measured from this family's own alignment rather than annotated, and only the fifteen most substituted are marked: every position carrying a minority substitution would be most of the protein, because the family holds orthologues. A residue can carry more than one and is drawn with the first that applies, in the order of the key above.

Primary citations

One record per paper, not per entry.

YearCitation
2026 The CASP 16 Experimental Protein-Ligand Datasets. Proteins doi:10.1002/prot.70053
2026 X-ray Diffraction Analyses of Trypsin Crystals Grown in the Presence of Additives Cryst.Growth Des. doi:10.1021/acs.cgd.5c01305
2026 A 3.3- angstrom cryo-EM structure of an engineered high-affinity human prothrombinase complex. Blood doi:10.1182/blood.2025031527
2026 N ‐Alkyl and N ‐Aryl Aminopyrazole Spirocarbamates: A Two-Pronged Lead Optimization Strategy to Identify Orally Bioavailable Plasma Kallikrein Inhibitors. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.6c00066
2026 Exosite-mediated targeting of GSDMB by dimeric granzyme A in lymphocyte pyroptotic killing. Immunity doi:10.1016/j.immuni.2025.12.009
2026 TMPRSS2-mediated coronavirus spike activation and inhibition. Nat.Struct.Mol.Biol. doi:10.1038/s41594-026-01801-y
2026 Complete inhibition of beta-tryptase by tetramer dissociation and active site allostery due to a single antibody residue. Nat Commun doi:10.1038/s41467-026-70491-3
2026 Anticoagulation with mechanistically distinct FXI/FXIa antibodies amrecibart (REGN9933A2) and cenvacibart (REGN7508Cat). Blood doi:10.1182/blood.2025032276
2026 Structural insights into the exosite-mediated activation of factor IX by factor XIa using cryogenic electron microscopy. J.Thromb.Haemost. doi:10.1016/j.jtha.2026.08.015
2026 Prothrombinase processivity is conferred by substrate allostery. Embo J. doi:10.1038/s44318-026-00782-4
2026 Structural requirements of blood factors binding to soluble hexon trimers with implications for adenovirus cell targeting and immune evasion. Plos Pathog. doi:10.1371/journal.ppat.1014389
2026 Molecular mechanism of cleavage at R271 during prothrombin activation revealed by cryo-EM. Blood doi:10.1182/blood.2025032364
2025 Large Library Docking and Biophysical Analysis of Small-Molecule TMPRSS2 Inhibitors. J.Med.Chem. doi:10.1021/acs.jmedchem.4c03089
2025 Structural basis of TMPRSS11D specificity and autocleavage activation. Nat Commun doi:10.1038/s41467-025-59677-3
2025 Discovery of an autoinhibited conformation in mesotrypsin reveals a strategy for selective serine protease inhibition. Sci Adv doi:10.1126/sciadv.adu9129
2025 Small molecule inhibitors of mannan-binding lectin-associated serine Proteases-2 and-3. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2025.117238
2025 Discovery and Preclinical Characterization of Fulacimstat (BAY 1142524), a Potent and Selective Chymase Inhibitor As a New Profibrinolytic Approach for Safe Thrombus Resolution. J.Med.Chem. doi:10.1021/acs.jmedchem.4c01819
2025 The crystal structure of coronavirus RBD-TMPRSS2 complex provides basis for the discovery of therapeutic antibodies. Nat Commun doi:10.1038/s41467-025-62023-2
2025 Integrating Surface Plasmon Resonance and Docking Analysis for Mechanistic Insights of Tryptase Inhibitors. Molecules doi:10.3390/molecules30061338
2025 The in vitro and crystallographic studies reveal the inhibitory potential of vitamin B 6 analogues against a serine protease trypsin. Int.J.Biol.Macromol. doi:10.1016/j.ijbiomac.2025.142433
2025 Discovery of BAY 3389934 Hydrochloride: A Potent and Selective Small-Molecule Dual Factor IIa/Xa Inhibitor with Short Half-Life for the Acute Treatment of Sepsis-Induced Coagulopathy. J.Med.Chem. doi:10.1021/acs.jmedchem.5c00538
2025 Structural determination of a new non-canonical inhibition complex between porcine trypsin and M271 a potato Kunitz-STI inhibitor. Biochem.Biophys.Res.Commun. doi:10.1016/j.bbrc.2025.151818
2025 Screening macrocyclic peptide libraries by yeast display allows control of selection process and affinity ranking. Nat Commun doi:10.1038/s41467-025-60907-x
2025 Molecular basis of vitamin K-dependent protein gamma-glutamyl carboxylation. Cell Res. doi:10.1038/s41422-025-01185-6
2025 Cryo-EM structure of coagulation factor Va bound to activated protein C. Blood doi:10.1182/blood.2025028476
2025 Monoclonal antibodies against human TMPRSS2 prevent infection by any SARS-CoV-2 variant. Iscience doi:10.1016/j.isci.2025.113424
2025 A TMPRSS6-inhibiting mAb improves disease in a beta-thalassemia mouse model and reduces iron in healthy humans. JCI Insight doi:10.1172/jci.insight.191813
2025 Cryo-EM structure of the tissue factor/factor VIIa complex with a factor X mimetic reveals a novel allosteric mechanism. Blood doi:10.1182/blood.2025029430
2025 A surface lipoprotein on Pasteurella multocida binds complement factor I to promote immune evasion. Plos Pathog. doi:10.1371/journal.ppat.1012686
2024 Mechanism-Based Macrocyclic Inhibitors of Serine Proteases. J.Med.Chem. doi:10.1021/acs.jmedchem.3c02388
2024 Use of protease substrate specificity screening in the rational design of selective protease inhibitors with unnatural amino acids: Application to HGFA, matriptase, and hepsin. Protein Sci. doi:10.1002/pro.5110
2024 Alternative Linkage Chemistries in the Chemoenzymatic Synthesis of Microviridin-Based Cyclic Peptides. Org.Lett. doi:10.1021/acs.orglett.3c04045
2024 Water-medicated specifically targeting the S1 pockets among serine proteases using an arginine analogue. Bioorg.Chem. doi:10.1016/j.bioorg.2024.107734
2024 Structural basis of TMPRSS2 zymogen activation and recognition by the HKU1 seasonal coronavirus. Cell doi:10.1016/j.cell.2024.06.007
2024 An RNA aptamer exploits exosite-dependent allostery to achieve specific inhibition of coagulation factor IXa. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2401136121
2024 S. aureus Eap is a polyvalent inhibitor of neutrophil serine proteases. J.Biol.Chem. doi:10.1016/j.jbc.2024.107627
2024 Structural basis for the binding of famotidine, cimetidine, guanidine, and pimagedine with serine protease. Biochem.Biophys.Res.Commun. doi:10.1016/j.bbrc.2024.150603
2024 Kunitz-type trypsin inhibitor from durian (Durio zibethinus) employs a distinct loop for trypsin inhibition. Protein Sci. doi:10.1002/pro.5230
2024 Macrocyclic Inhibitors Targeting the Prime Site of the Fibrinolytic Serine Protease Plasmin. Chemmedchem doi:10.1002/cmdc.202400360
2024 Crystal structure of the Michaelis complex of trypsin with N-alpha-benzoyl-l-arginine ethyl ester J Chin Chem Soc doi:10.1002/jccs.202400214