Hirudin

From Wikipedia, the free encyclopedia

Structure of Hirudin in complex with Thrombin.[1]

Hirudine

crystallographic analysis at 3.0-angstroms resolution

of the binding to human thrombin of four active site-
directed inhibitors
Identifiers
Symbol Hirudin
Pfam PF00713
InterPro IPR000429
SCOP 4htc
SUPERFAMILY 4htc
[show]Available protein structures:

Hirudin is a naturally occurring peptide in the salivary glands of medicinal leeches (such as
Hirudo medicinalis) that has a blood anticoagulant property. This is fundamental for the leeches’
alimentary habit of hematophagy, since it keeps the blood flowing after the initial phlebotomy
performed by the worm on the host’s skin.

Contents
 1 Structure
  2 Biological activity
 3 See also
 4 References
 5 External links

Structure
During his years in Birmingham and Edinburgh, John Berry Haycraft had been actively engaged
in research and published papers on the coagulation of blood, and in 1884, he discovered that the
leech secreted a powerful anticoagulant, which he named hirudin, although it was not isolated
until the 1950s, nor its structure fully determined until 1976. Full length hirudin is made up of 65
amino acids. These amino acids are organised into a compact N-terminal domain containing
three disulfide bonds and a C-terminal domain that is completely disordered when the protein is
un-complexed in solution.[2][3] Amino acid residues 1-3 form a parallel beta- strand with residues
214-217 of thrombin, the nitrogen atom of residue 1 making a hydrogen bond with the Ser-195 O
gamma atom of the catalytic site. The C-terminal domain makes numerous electrostatic
interactions with an anion-binding exosite of thrombin, while the last five residues are in a
helical loop that forms many hydrophobic contacts.[4] Natural hirudin contains a mixture of
various isoforms of the protein. However, recombinant techniques can be used to produce
homogeneous preparations of hirudin.[5]

Biological activity
A key event in the final stages of blood coagulation is the conversion of fibrinogen into fibrin by
the serine protease enzyme thrombin.[6] Thrombin is produced from prothrombin, by the action of
an enzyme, prothrombinase (Factor Xa along with Factor Va as a cofactor), in the final states of
coagulation. Fibrin is then cross linked by factor XIII (Fibrin Stabilizing Factor) to form a blood
clot. The principal inhibitor of thrombin in normal blood circulation is antithrombin.[5] Similar to
antithrombin III, the anticoagulatant activity of hirudin is based on its ability to inhibit the
procoagulant activity of thrombin.

Hirudin is the most potent natural inhibitor of thrombin. Unlike antithrombin, hirudin binds to
and inhibits only the activity of thrombin, with a specific activity on fibrinogen.[5] Therefore,
hirudin prevents or dissolves the formation of clots and thrombi (i.e., it has a thrombolytic
activity), and has therapeutic value in blood coagulation disorders, in the treatment of skin
hematomas and of superficial varicose veins, either as an injectable or a topical application
cream. In some aspects, hirudin has advantages over more commonly used anticoagulants and
thrombolytics, such as heparin, as it does not interfere with the biological activity of other serum
proteins, and can also act on complexed thrombin.

It is difficult to extract large amounts of hirudin from natural sources, so a method for producing
and purifying this protein using recombinant biotechnology has been developed. This has led to
the development and marketing of a number of hirudin-based anticoagulant pharmaceutical
products, such as lepirudin (Refludan), hirudin derived from Hansenula (Thrombexx, Extrauma)
and desirudin (Revasc/Iprivask). Several other direct thrombin inhibitors are derived chemically
from hirudin.

See also
 Hirudotherapy
 Discovery and Development of Direct Thrombin Inhibitors

References
1. Jump up ^ PDB 4HTC
2. Jump up ^ Folkers PJM, Clore GM. et al. (1989). "Solution structure of recombinant
hirudin and the Lys-47-Glu mutant: a nuclear magnetic resonance and hybrid distance
geometry-dynamical simulated annealing study". Biochemistry 28 (6): 2601–2617.
doi:10.1021/bi00432a038. PMID 2567183.
3. Jump up ^ Haruyama H. and Wuthrich K. (1989). "Conformation of recombinant
desulfatohirudin in aqueous solution determined by nuclear magnetic resonance".
Biochemistry 28 (10): 4301–4312. doi:10.1021/bi00436a027. PMID 2765488.
4. Jump up ^ Rydel TJ, Ravichandran KG, Tulinsky A, Bode W, Huber R, Roitsch C,
Fenton JW (July 1990). "The structure of a complex of recombinant hirudin and human
alpha-thrombin". Science 249 (4966): 277–80. doi:10.1126/science.2374926.
PMID 2374926.
5. ^ Jump up to: a b c Rydell TJ, Tulinsky A. et al. (1991). "Refined structure of the Hirudin-
Thrombin complex". J. Mol. Biol. 221 (2): 583–601. doi:10.1016/0022-2836(91)80074-5.
PMID 1920434.
6. Jump up ^ Fenton JW 2nd, Ofosu SA et al. (1998). "Thrombin and antithrombotics".
Semin Thromb Hemost 24 (2): 87–91. doi:10.1055/s-2007-995828. PMID 9579630.
Zat-zat Penuh Manfaat yang Terkandung dalam Lintah
Desember 11, 2009 — eNHa Farm
 
 
 
 
 
 
18 Votes

Dari hasil kajian-kajian dan penelitian ilmiah yang dilakukan, telah diketahui bahwa lintah
mengandung banyak zat yang penuh manfaat bagi tubuh manusia. Berikut ini antara lain zat-zat
yang terkandung di dalam lintah:

Nitric Oxide: pada tahun 1998 Hadiah Nobel untuk fisiologi telah dianugerahkan kepada Robert
Furchgott, Prof Louis Ignarro dan Ferid Murad yang menemukan pertalian Nitric Oxide (NO)
yang kemudian digunakan dalam ramuan Viagra. Dalam satu kajian ilmiah Universiti Purdue,
lintah jenis Hirudo Medicinalis dikenal dapat mengeluarkan NO secara alami. Sementara kajian
ilmah lainnya mengatakan bahwa NO dapat menyelesaikan 90% masalah kegagalan ereksi kaum
lelaki. Vagina dan klitoris wanita apabila tersentuh oleh usur NO ini juga dapat meningkatkan
rangsangan seksual, dimana NO tersebut akan memberi stimulus ke syaraf-syaraf yang memacu
gairah seksual wanita.

Ilustrasi ikatan kimia Hirudin

Hirudin: adalah zat yang dapat menghalang pembekuan darah. Umumnya digunakan untuk
membuat darah tetap mengalir tidak membeku, unsur Hirudo medicinalis dipakai dalam operasi
syaraf-syaraf yang kecil, misalnya operasi pada telapak tangan, untuk mengembalikan aliran
darah yang buntu atau saluran darah yang tersumbat.
Hirudin terdiri dari 65 Asam amino yang berpotensi, menghambat pendarahan atau pembekuan
darah. Hirudin akan mengurangi gumpalan darah yang terbentuk dan meningkatkan aliran darah
pada bagian-bagian tertentu dalam tubuh kita.

Histamine: adalah zat yang berfungsi sebagai pengembang. Zat pengembang ini di temukan
pada bagian ludah lintah.

Hyaluronidase: Zat yang berasal dari ludah lintah yang termasuk dalam jenis obat bius,
pencegah pembekuan darah (hirudin), vasodilator lokal (histamine) dan satu enzim
(hyaluronidase).

Thrombin : Zat yang mengaktifkan konversi dari fibrin dari fibrinogen dan meningkatkan
pembekuan. Trombosa adalah formasi dari satu gumpal darah di dalam satu pembuluh darah,
yang sering menghalangi aliran darah. Trombosa akan terjadi apa bila tubuh mengalami luka.
Lokasi paling umum dari trombosa berada di dalam pembuluh darah dari kaki.

Anti Kolagen: zat yang keluar dari air liur lintah atau spesies sejenis berdasarkan hasil penelitian
ternyata dapat digunakan untuk perawatan dan pengendalian trombosit. Zat ini dapat berfungsi
sebagai penunda penuaan dan dapat digunakan sebagai bagian bahan dasar kosmetika.

Tak disangka ternyata mahluk kecil yang bagi sebagian orang dianggap menjijikkan ternyata
mengandung begitu banyak zat yang penuh manfaat bagi kita. Mari kita manfaatkan lintah demi
kebaikan dan kesehatan kita semua!