PDBsum entry 2d1j

Hydrolase

PDB id

2d1j

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Contents

			Protein chains

					233 a.a. *


					54 a.a. *

			Ligands

					D01

			Metals

					_CA ×2

			Waters ×111

* Residue conservation analysis

PDB id:

2d1j

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Name:

Hydrolase

Title:

Factor xa in complex with the inhibitor 2-[[4-[(5-chloroindol-2-yl) sulfonyl]piperazin-1-yl] carbonyl]thieno[3,2-b]pyridine n-oxide

Structure:

Coagulation factor x, heavy chain. Chain: a. Fragment: residues 16-243. Synonym: stuart factor, stuart-prower factor. Coagulation factor x, light chain. Chain: b. Fragment: residues 85-138. Synonym: stuart factor, stuart-prower factor. Ec: 3.4.21.6

Source:

Homo sapiens. Human. Organism_taxid: 9606. Other_details: proteolytic cleavage product

Biol. unit:

Dimer (from PQS)

Resolution:

2.20Å

R-factor:

0.188

R-free:

0.232

Authors:

M.Suzuki

Key ref:

S.Komoriya et al. (2005). Design, synthesis, and biological activity of non-basic compounds as factor Xa inhibitors: SAR study of S1 and aryl binding sites. Bioorg Med Chem Lett, 13, 3927-3954. PubMed id: 15911309

Date:

24-Aug-05

Release date:

24-Aug-06

PROCHECK

	Headers

	References

Protein chain

P00742 (FA10_HUMAN) - Coagulation factor X from Homo sapiens

Seq: Struc:					488 a.a. 233 a.a.

Protein chain

P00742 (FA10_HUMAN) - Coagulation factor X from Homo sapiens

Seq: Struc:					488 a.a. 54 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

Chains A, B: E.C.3.4.21.6 - coagulation factor Xa.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

Preferential cleavage: Arg-|-Thr and then Arg-|-Ile bonds in prothrombin to form thrombin.

	Bioorg Med Chem Lett 13:3927-3954 (2005)
PubMed id: 15911309

Design, synthesis, and biological activity of non-basic compounds as factor Xa inhibitors: SAR study of S1 and aryl binding sites.
S.Komoriya, N.Haginoya, S.Kobayashi, T.Nagata, A.Mochizuki, M.Suzuki, T.Yoshino, H.Horino, T.Nagahara, M.Suzuki, Y.Isobe, T.Furugoori.

ABSTRACT

Compound 7 was identified as the active metabolite of 6 by HPLC and mass spectral analysis. Modification of lead compound 7 by transformation of its N-oxide 6-6 biaryl ring system and fused aromatics produced a series of non-basic fXa inhibitors with excellent potency in anti-fXa and anticoagulant assays. The optimized compounds 73b and 75b showed sub to one digit micromolar anticoagulant activity (PTCT2). Particularly, anti-fXa activity was detected in plasma of rats orally administered with 1mg/kg of compound 75b.

Literature references that cite this PDB file's key reference

PubMed id

Reference

19967784

Y.K.Lee, and M.R.Player (2011).
Developments in factor Xa inhibitors for the treatment of thromboembolic disorders.

Med Res Rev, 31, 202-283.

18077174

Y.Imaeda, T.Miyawaki, H.Sakamoto, F.Itoh, N.Konishi, K.Hiroe, M.Kawamura, T.Tanaka, and K.Kubo (2008).
Discovery of sulfonylalkylamides: A new class of orally active factor Xa inhibitors.

Bioorg Med Chem, 16, 2243-2260.

17683371

J.T.Kohrt, C.F.Bigge, J.W.Bryant, A.Casimiro-Garcia, L.Chi, W.L.Cody, T.Dahring, D.A.Dudley, K.J.Filipski, S.Haarer, R.Heemstra, N.Janiczek, L.Narasimhan, T.McClanahan, J.T.Peterson, V.Sahasrabudhe, R.Schaum, C.A.Van Huis, K.M.Welch, E.Zhang, R.J.Leadley, and J.J.Edmunds (2007).
The discovery of (2R,4R)-N-(4-chlorophenyl)-N- (2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)-4-methoxypyrrolidine-1,2-dicarboxamide (PD 0348292), an orally efficacious factor Xa inhibitor.

Chem Biol Drug Des, 70, 100-112.

PDB code:

2phb

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.