1JMO	Blood Clotting	date	Jul 19, 2001
title	Crystal Structure Of The Heparin Cofactor II-S195a Thrombin Complex
authors	T.P.Baglin, R.W.Carrell, F.C.Church, C.T.Esmon, J.A.Huntington
compound		source
Molecule: Thrombin, Light Chain Chain: L Fragment: Light Chain Synonym: Coagulation Factor II Engineered: Yes Other_details: Contains Extra 13 Amino Acids At The N- Terminus;		Organism_scientific: Homo Sapiens Organism_common: Human Expression_system: Cricetulus Griseus Expression_system_common: Chinese Hamster Expression_system_cell_line: Bhk Culture Expression_system_organ: Kidney
Molecule: Thrombin, Heavy Chain Chain: H Fragment: Heavy Chain Synonym: Coagulation Factor II Ec: 3.4.21.5 Engineered: Yes Mutation: Yes		Organism_scientific: Homo Sapiens Organism_common: Human Expression_system: Cricetulus Griseus Expression_system_common: Chinese Hamster Expression_system_cell_line: Bhk Culture Expression_system_organ: Kidney
Molecule: Heparin Cofactor II Chain: A Synonym: Hc-II; Protease Inhibitor Leuserpin 2; Hls2 Serine (Or Cysteine) Proteinase Inhibitor, Clade D (Heparin Cofactor), Member 1		Organism_scientific: Homo Sapiens Organism_common: Human Other_details: Plasma Purified Human Heparin Cofactor II
symmetry	Space Group: P 61	R_factor	0.205
crystal cell	length a length b length c angle alpha angle beta angle gamma 152.310 152.310 126.800 90.00 90.00 120.00
method	X-Ray Diffraction	resolution	2.20 Å
ligand	STY, NAG, MPD	enzyme	Thrombin. Fibrinogenase. Thrombase. Thrombofort. Topical. Thrombin-C. Tropostasin. Activated blood-coagulation factor II. Blood-coagulation factor IIa. Factor IIa. E thrombin. Beta-thrombin. Gamma-thrombin. Hydrolase E.C.3.4.21.5
note	1JMO is a representative structure
related structures	by homologous chain: 1JMJ, 1NU7, 1QHR
domain	The n-terminal acidic repeat region mediates, in part, the glycosaminoglycan-accelerated thrombin inhibition.
similarity	Contains 2 kringle domains. Belongs to peptidase family s1. Belongs to the serpin family.[trypsin]
catalytic activ.	Preferential cleavage fibrinogen to fibrin and releases fibrinopeptide a and b.
post-translat. modifications	The gamma-carboxyglutamyl residues, which bind calcium ions, result from the carboxylation of glutamyl residues by a microsomal enzyme, the vitamin k-dependent carboxylase. The modified residues are necessary for the calcium-dependent interaction with a negatively charged phospholipid surface, which is essential for the conversion of prothrombin to thrombin.
tissue	Expressed predominantly in liver. Expressed by the liver and secreted in plasma.
subcellular loc.	Extracellular.
genes	F2 (B. taurus); B2209, ECO, ETI (E. coli); F2, HCF2, SERPIND1, THBD, THRM (H. sapiens)
function	Thrombin, which cleaves bonds after arg and lys, converts fibrinogen to fibrin and activates factors v, vii, viii, xiii, and, in complex with thrombomodulin, protein c. Also inhibits chymotrypsin, but in a glycosaminoglycan-independent manner. In the presence of the latter, hc-ii becomes the predominant thrombin inhibitor in place of antithrombin iii (at-iii). Peptides at the n-terminal of hc-ii have chemotactic activity for both monocytes and neutrophils. Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate.
Gene Ontology	chain A: GO:0004866, GO:0004867, GO:0005576, GO:0006935, GO:0007596, GO:0008201 chain H: GO:0000074, GO:0003809, GO:0004252, GO:0004263, GO:0004295, GO:0005102, GO:0005509, GO:0005576, GO:0005615, GO:0005625, GO:0006508, GO:0006915, GO:0006919, GO:0006953, GO:0007260, GO:0007262, GO:0007275, GO:0007596, GO:0008236, GO:0009611, GO:0016787, GO:0030168, GO:0030193, GO:0042730 chain L: GO:0000074, GO:0003809, GO:0004252, GO:0004263, GO:0004295, GO:0005102, GO:0005509, GO:0005576, GO:0005615, GO:0005625, GO:0006508, GO:0006915, GO:0006919, GO:0006953, GO:0007260, GO:0007262, GO:0007275, GO:0007596, GO:0008236, GO:0009611, GO:0016787, GO:0030168, GO:0030193, GO:0042730
disease	Dysprothrombinemia Hyperprothrombinemia Hypoprothrombinemia Thrombophilia due to heparin cofactor II deficiency Myocardialinfarction,susceptibility to Thrombophilia due to thrombomodulin defect Hcf-ii deficiency is a form of thrombophilia [mim. 188050], an autosomal dominant disorder in which affected individuals are prone to develop serious spontaneous thrombosis. Defects in f2 are the cause of various forms of dysprothrombinemia [mim. 176930]. Defects in serpind1 are the cause of heparin cofactor ii deficiency (hcf-ii deficiency) [mim. 142360, 188050].
Primary reference	Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism., Baglin TP, Carrell RW, Church FC, Esmon CT, Huntington JA, Proc Natl Acad Sci U S A 2002 Aug 20;99(17):11079-84. PMID:12169660

Data retrieval

Asymmetric unit, PDB entry: [header only] [complete with coordinates] (150 Kb) [Save to disk] Biological Unit Coordinates (1jmo.pdb1.gz) 129 Kb LPC: Ligand-Protein Contacts for 1JMO CSU: Contacts of Structural Units for 1JMO Likely Quarternary Molecular Structure file(s) for 1JMO Structure Factors (r1jmosf.ent.Z) 798 Kb Retrieve 1JMO in mmCIF format [Save to disk]

View 1JMO in 3D

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Visual 3D analysis of 1JMO

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Structure-derived information

Electro Density related parameters from EDS Electron Density Server, at Upsala Dipole moment, from Dipole Server at Weizmann Institute Crystal Contacts, from CryCo at Weizmann Institute Classification of representative domains in scop (Structural Classification of Proteins)     - Domain d1jmoa_, region A [Jmol] [rasmolscript] [script source]     - Domain d1jmo.1, region L:,H [Jmol] [rasmolscript] [script source] Fold representative 1jmo from FSSP and Dali (Families of Structurally Similar Proteins)

Sequence-derived information

View one-letter amino acid or nucleotide sequence for each chain: [1jmo_H] [1jmo_A] [1jmo_L] SWISS-PROT database: [P05546] [P00734] Domain organization of [THRB_HUMAN] [HEP2_HUMAN] by SWISSPFAM Conserved protein region description, domain view and alignment from family trypsin (PF00089) of Pfam. Alignments of the sequence of 1JMO with the sequences similar proteins can be viewed for classification [THRB_HUMAN] [HEP2_HUMAN] at ProtoMap. Click on "Neighbors List", then on the "See Alignments" button below the list. A sequence distance tree ("phylogenetic tree") can be viewed for 1ACL's classification [THRB_HUMAN] [HEP2_HUMAN] at ProtoMap. Click on the Cluster number.

Other resources with information on 1JMO

InterPro: IPR000001 , IPR001314 , IPR002383 , IPR009003 , IPR001254 , IPR003966 , IPR000294 , IPR000295 , IPR000215 PDBREPORT (protein verification by WHAT_CHECK procedures) MMDB (Entrez's Structure Database)

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