4X8G

Crystal structure of human peptidylarginine deiminase type4 (PAD4) in complex with GSK199

Summary for 4X8G

• Entry DOI: 10.2210/pdb4x8g/pdb
• Related: 4X8C
• Descriptor: Protein-arginine deiminase type-4, CALCIUM ION, [(3R)-3-aminopiperidin-1-yl][2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzimidazol-5-yl]methanone, ... (4 entities in total)
• Functional Keywords: hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: Q9UM07
• Total number of polymer chains: 1
• Total formula weight: 75510.67

Authors

Lewis, H.D.,Bax, B.D.,Chung, C.-W.,Polyakova, O.,Thorpe, J. (deposition date: 2014-12-10, release date: 2015-01-28, Last modification date: 2024-02-28)

Primary citation

Lewis, H.D.,Liddle, J.,Coote, J.E.,Atkinson, S.J.,Barker, M.D.,Bax, B.D.,Bicker, K.L.,Bingham, R.P.,Campbell, M.,Chen, Y.H.,Chung, C.W.,Craggs, P.D.,Davis, R.P.,Eberhard, D.,Joberty, G.,Lind, K.E.,Locke, K.,Maller, C.,Martinod, K.,Patten, C.,Polyakova, O.,Rise, C.E.,Rudiger, M.,Sheppard, R.J.,Slade, D.J.,Thomas, P.,Thorpe, J.,Yao, G.,Drewes, G.,Wagner, D.D.,Thompson, P.R.,Prinjha, R.K.,Wilson, D.M.
Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation.
Nat.Chem.Biol., 11:189-191, 2015

PubMed Abstract: PAD4 has been strongly implicated in the pathogenesis of autoimmune, cardiovascular and oncological diseases through clinical genetics and gene disruption in mice. New selective PAD4 inhibitors binding a calcium-deficient form of the PAD4 enzyme have validated the critical enzymatic role of human and mouse PAD4 in both histone citrullination and neutrophil extracellular trap formation for, to our knowledge, the first time. The therapeutic potential of PAD4 inhibitors can now be explored.

PubMed: 25622091
DOI: 10.1038/nchembio.1735

Experimental method

X-RAY DIFFRACTION (3.29 Å)