RSS

PDB:1P1M

Protein Name

Amidohydrolase Tm0936

Species

Thermotoga maritima

Biological Context

The amidohydrolase superfamily (AHS) has about 6,000 member proteins, which catalyses the hydrolysis of an amide group. All of them adopt a common (β/α) 8-barrel fold and almost all are metallo-enzymes.

Tm0936, a member of AHS from Thermotoga maritima, acts as a 5-methyltioadenosine (MTA)/S-adenosylhomocysteine (SAH) deaminase to catalysis a deamination reaction. MTA, SAH, adenosine, AMP, and S-adenosylmethionine (SAM, which is similar to SAH) were tested as substrates. Activity was observed for the first three molecules. MTA becomes MTI (Fig. 1), SAH becomes SIH (Fig. 2) and adenosine becomes inosine by the deamination. However, the remaining AMP and SAM were not deaminated.

Although it is not yet confirmed, Tm0936 may be involved in the deamination of metabolites in a previously uncharacterized MTA/SAH pathway. Indeed, S-adenosyl homocysteinase (Tm0172) was shown to catalyze the formation of homocysteine from either SIH or SAH about equally well, and both enzymes could thus participate together in the degradation of SHA to homocysteine and inosine.

MTAtoMTI
(Fig. 1) Deamination of MTA to MTI.

Left, 5-methylthioadenosine (MTA).
Right, 5-methylthioinosine (MTI).
SAHtoSIH
(Fig. 2) Deamination of SAH to SIH.

Left, S-adenosylhomocysteine (SAH).
Right, S-inosylhomocysteine (SIH).

Structure Description

1p1m1p1m_x1p1m_y

Tm0936 was initially crystallized as a hypothetical protein with unknown substrate preference (this PDB id, 1P1M). After that, a complex of SIH-Tm0936 has been solved (xPSSS:2PLM), showing that Tm0936 acts as an MTA/SAH deaminase. Tm0936 has a (β/α) 8-barrel fold with a metal ion (Ni2+ in 1P1M, Zn2+ in 2PLM) near the substrate-binding region. The substrate was surrounded by the side-chains of histidine, arginine, and glutamic acid.

Further understanding of how Tm0936 works together with the other enzymes and to which metabolic pathways it belongs are expected.

structure (Fig. 3) Tm0936 in complex with SIH.

The PDB ID is 2PLM (xPSSS:2PLM).
The substrate SIH is shown as red.
Tm0936 is gray,the side-chains near SIH are green.
A zinc ion (Zn2+) is the blue sphere.

Protein Data Bank (PDB)

References

Source

Kniewel, R. Buglino, J.A. Lima, C.D.; "Structure of the hypothetical protein TM0936 from Thermotoga maritima at 1.5A bound to Ni and methionine"; To be Published; (2003) :-.

Others

author: Naoya Fujita


Japanese version:PDB:1P1M