PDBsum entry 1zml

Transferase

PDB id: 1zml

Contents

Protein chain

237 a.a. *

Ligands

SO4 ×6

BCT

412

Waters ×181

* Residue conservation analysis

PDB id:

1zml

Name:

Transferase

Title:

Crystal structure of the catalytic domain of factor xi in complex with (r)-1-(4-(4-(hydroxymethyl)-1,3,2-dioxaborolan-2-yl)phenethyl) guanidine

Structure:

Coagulation factor xi. Chain: a. Fragment: catalytic domain. Synonym: plasma thromboplastin antecedent, pta, fxi. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: f11. Expressed in: pichia pastoris. Expression_system_taxid: 4922.

Resolution:

2.25Å R-factor: 0.203 R-free: 0.229

Authors:

T.I.Lazarova,L.Jin,M.J.Rynkiewicz,J.C.Gorga,F.Bibbins,H.V.Meyers, R.E.Babine,J.E.Strickler

Key ref:

T.I.Lazarova et al. (2006). Synthesis and in vitro biological evaluation of aryl boronic acids as potential inhibitors of factor XIa. Bioorg Med Chem Lett, 16, 5022-5027. PubMed id: 16876411 DOI: 10.1016/j.bmcl.2006.07.043

Date:

10-May-05 Release date: 09-May-06

Protein chain

P03951  (FA11_HUMAN) -  Coagulation factor XI from Homo sapiens

Seq: 625 a.a.

Struc: 237 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.4.21.27 - coagulation factor XIa.
• Reaction: Selective cleavage of Arg-|-Ala and Arg-|-Val bonds in factor IX to form factor IXa.

DOI no: 10.1016/j.bmcl.2006.07.043

Bioorg Med Chem Lett 16:5022-5027 (2006)

PubMed id: 16876411

Synthesis and in vitro biological evaluation of aryl boronic acids as potential inhibitors of factor XIa.

T.I.Lazarova, L.Jin, M.Rynkiewicz, J.C.Gorga, F.Bibbins, H.V.Meyers, R.Babine, J.Strickler.

ABSTRACT

A series of functionalized aryl boronic acids were synthesized and evaluated as potential inhibitors of factor XIa. Crystal structures of the protein-inhibitor complexes led to the design and synthesis of second generation compounds showing single digit micromolar inhibition against FXIa and selectivity against thrombin, trypsin, and FXa.