Proteins: Structure, Function and Bioinformatics 2002-02-15

Structure and cooperativity of a T-state mutant of histidine decarboxylase from Lactobacillus 30a.

Scott Worley, Elisabeth Schelp, Arthur F Monzingo, Stephen Ernst, Jon D Robertus

Index: Proteins 46(3) , 321-9, (2002)

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Abstract

Histidine decarboxylase (HDC) from Lactobacillus 30a converts histidine to histamine, a process that enables the bacteria to maintain the optimum pH range for cell growth. HDC is regulated by pH; it is active at low pH and inactive at neutral to alkaline pH. The X-ray structure of HDC at pH 8 revealed that a helix was disordered, resulting in the disruption of the substrate-binding site. The HDC trimer has also been shown to exhibit cooperative kinetics at neutral pH, that is, histidine can trigger a T-state to R-state transition. The D53,54N mutant of HDC has an elevated Km, even at low pH, indicating that the enzyme assumes the low activity T-state. We have solved the structures of the D53,54N mutant at low pH, with and without the substrate analog histidine methyl ester (HME) bound. Structural analysis shows that the apo-D53,54N mutant is in the inactive or T-state and that binding of the substrate analog induces the enzyme to adopt the active or R-state. A mechanism for the cooperative transition is proposed.Copyright 2002 Wiley-Liss, Inc.