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A synthetic protein selected for ligand binding affinity mediates ATP hydrolysis.

Abstract：

:How primitive enzymes emerged from a primordial pool remains a fundamental unanswered question with important practical implications in synthetic biology. Here we show that a de novo evolved ATP binding protein, selected solely on the basis of its ability to bind ATP, mediates the regiospecific hydrolysis of ATP to ADP when crystallized with 1 equiv of ATP. Structural insights into this reaction were obtained by growing protein crystals under saturating ATP conditions. The resulting crystal structure refined to 1.8 A resolution reveals that this man-made protein binds ATP in an unusual bent conformation that is metal-independent and held in place by a key bridging water molecule. Removal of this interaction using a null mutant results in a variant that binds ATP in a normal linear geometry and is incapable of ATP hydrolysis. Biochemical analysis, including high-resolution mass spectrometry performed on dissolved protein crystals, confirms that the reaction is accelerated in the crystalline environment. This observation suggests that proteins with weak chemical reactivity can emerge from high affinity ligand binding sites and that constrained ligand-binding geometries could have helped to facilitate the emergence of early protein enzymes.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Simmons CR,Stomel JM,McConnell MD,Smith DA,Watkins JL,Allen JP,Chaput JC

doi

10.1021/cb900109w

subject

Has Abstract

pub_date

2009-08-21 00:00:00

pages

649-58

issue

8

eissn

1554-8929

issn

1554-8937

journal_volume

4

pub_type

杂志文章

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