5EYG

Crystal structure of IMPase/NADP phosphatase complexed with NADP and Ca2+

Replaces:  4G62

Summary for 5EYG

• Entry DOI: 10.2210/pdb5eyg/pdb
• Related: 5EYH
• Descriptor: Inositol monophosphatase, CALCIUM ION, TRIETHYLENE GLYCOL, ... (9 entities in total)
• Functional Keywords: impase, fig superfamily, phosphatase, substrate bound complex, hydrolase
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 63473.70

Authors

Bhattacharyya, S.,Dutta, D.,Ghosh, A.K.,Das, A.K. (deposition date: 2015-11-25, release date: 2015-12-23, Last modification date: 2023-11-08)

Primary citation

Bhattacharyya, S.,Dutta, A.,Dutta, D.,Ghosh, A.K.,Das, A.K.
Structural elucidation of the NADP(H) phosphatase activity of staphylococcal dual-specific IMPase/NADP(H) phosphatase
Acta Crystallogr D Struct Biol, 72:281-290, 2016

PubMed Abstract: NADP(H)/NAD(H) homeostasis has long been identified to play a pivotal role in the mitigation of reactive oxygen stress (ROS) in the intracellular milieu and is therefore critical for the progression and pathogenesis of many diseases. NAD(H) kinases and NADP(H) phosphatases are two key players in this pathway. Despite structural evidence demonstrating the existence and mode of action of NAD(H) kinases, the specific annotation and the mode of action of NADP(H) phosphatases remains obscure. Here, structural evidence supporting the alternative role of inositol monophosphatase (IMPase) as an NADP(H) phosphatase is reported. Crystal structures of staphylococcal dual-specific IMPase/NADP(H) phosphatase (SaIMPase-I) in complex with the substrates D-myo-inositol-1-phosphate and NADP(+) have been solved. The structure of the SaIMPase-I-Ca(2+)-NADP(+) ternary complex reveals the catalytic mode of action of NADP(H) phosphatase. Moreover, structures of SaIMPase-I-Ca(2+)-substrate complexes have reinforced the earlier proposal that the length of the active-site-distant helix α4 and its preceding loop are the predisposing factors for the promiscuous substrate specificity of SaIMPase-I. Altogether, the evidence presented suggests that IMPase-family enzymes with a shorter α4 helix could be potential candidates for previously unreported NADP(H) phosphatase activity.

PubMed: 26894675
DOI: 10.1107/S2059798316000620

Experimental method

X-RAY DIFFRACTION (2.2 Å)