5FWQ

Apo structure of human Leukotriene A4 hydrolase

Summary for 5FWQ

• Entry DOI: 10.2210/pdb5fwq/pdb
• Descriptor: HUMAN LEUKOTRIENE A4 HYDROLASE, ACETATE ION, ZINC ION, ... (6 entities in total)
• Functional Keywords: hydrolase, leukotriene (lt) a4 hydrolase/aminopeptidase, lta4h
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 73186.66

Authors

Wittmann, S.K.,Kalinowsky, L.,Kramer, J.,Bloecher, R.,Steinhilber, D.,Pogoryelov, D.,Proschak, E.,Heering, J. (deposition date: 2016-02-19, release date: 2016-10-05, Last modification date: 2024-01-10)

Primary citation

Wittmann, S.K.,Kalinowsky, L.,Kramer, J.S.,Bloecher, R.,Knapp, S.,Steinhilber, D.,Pogoryelov, D.,Proschak, E.,Heering, J.
Thermodynamic properties of leukotriene A4hydrolase inhibitors.
Bioorg.Med.Chem., 24:5243-5248, 2016

PubMed Abstract: The leukotriene A hydrolase (LTAH) is a bifunctional enzyme, containing a peptidase and a hydrolase activity both activities having opposing functions regulating inflammatory response. The hydrolase activity is responsible for the conversion of leukotriene A to pro-inflammatory leukotriene B, and hence, selective inhibitors of the hydrolase activity are of high pharmacological interest. Here we present the thermodynamic characterization of structurally distinct inhibitors of the LTAH that occupy different regions of the binding site using different biophysical methods. An in silico method for the determination of stabilized water molecules in the binding site of the apo structure of LTAH is used to interpret the measured thermodynamic data and provided insights for design of novel LTAH inhibitors.

PubMed: 27651294
DOI: 10.1016/j.bmc.2016.08.047

Experimental method

X-RAY DIFFRACTION (2.047 Å)