PDBsum entry 1kye

Hydrolase

PDB id

1kye

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Contents

			Protein chains

					234 a.a. *


					51 a.a. *

			Ligands

					RUP

			Metals

					_CA ×2

			Waters ×124

* Residue conservation analysis

Obsolete entry

PDB id:

1kye

Links
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Name:

Hydrolase

Title:

Factor xa in complex with (r)-2-(3-adamantan-1-yl-ureido)-3- (3-carbamimidoyl-phenyl)-n-phenethyl-propionamide

Structure:

Factor xa. Chain: a. Fragment: factor xa heavy chain. Synonym: coagulation factor x. Factor xa. Chain: b. Fragment: factor xa light chain. Synonym: coagulation factor x. Ec: 3.4.21.6

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organism_taxid: 9606

Biol. unit:

Dimer (from PQS)

Resolution:

2.22Å

R-factor:

0.223

R-free:

0.266

Authors:

M.M.Mueller,S.Sperl,J.Sturzebecher,W.Bode,L.Moroder

Key ref:

M.M.Mueller et al. (2002). (R)-3-Amidinophenylalanine-derived inhibitors of factor Xa with a novel active-site binding mode. Biol Chem, 383, 1185-1191. PubMed id: 12437104

Date:

04-Feb-02

Release date:

11-Feb-03

PROCHECK

	Headers

	References

Protein chain

P00742 (FA10_HUMAN) - Coagulation factor X from Homo sapiens

Seq: Struc:					488 a.a. 234 a.a.

Protein chain

P00742 (FA10_HUMAN) - Coagulation factor X from Homo sapiens

Seq: Struc:					488 a.a. 51 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

Chain A: 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.

	Biol Chem 383:1185-1191 (2002)
PubMed id: 12437104

(R)-3-Amidinophenylalanine-derived inhibitors of factor Xa with a novel active-site binding mode.
M.M.Mueller, S.Sperl, J.Stürzebecher, W.Bode, L.Moroder.

ABSTRACT

A putative non-substrate like binding mode of (R)-3-amidinophenylalanine derivatives to factor Xa, as derived from modeling experiments based on X-ray analysis of their complexes with trypsin, was used to design a new generation of inhibitors. However, the resulting inhibitory potencies were not at all consistent with the working assumption, although with an adamantyl-ureido derivative of (R)-3-amidinophenylalanine phenetyl amide a highly selective nanomolar inhibition of factor Xa was achieved. The X-ray analysis of the complex of this ligand with factor Xa revealed an unexpected new binding mode, of which the most important feature is the interaction of the C-terminal aryl moiety with a hydrophobic subregion of the S1 subsite, while the adamantyl group occupies the hydrophobic S3/S4 subsites of the enzyme.

Literature references that cite this PDB file's key reference

PubMed id

Reference

18680100

N.Singh, and J.M.Briggs (2008).
Molecular dynamics simulations of Factor Xa: insight into conformational transition of its binding subsites.

Biopolymers, 89, 1104-1113.

18266362

R.Abel, T.Young, R.Farid, B.J.Berne, and R.A.Friesner (2008).
Role of the active-site solvent in the thermodynamics of factor Xa ligand binding.

J Am Chem Soc, 130, 2817-2831.

16381925

P.Block, C.A.Sotriffer, I.Dramburg, and G.Klebe (2006).
AffinDB: a freely accessible database of affinities for protein-ligand complexes from the PDB.

Nucleic Acids Res, 34, D522-D526.

15988604

K.Schrör (2005).
[Haemostaseology]

Internist (Berl), 46, 873.

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.