Further Evidence for a Separate Enzymic Entity for the
Synthesis of Homocitrulline, Distinct from the Regular
Ornithine Transcarbamylase

Al, Carter; Ag, Eller; Rufo, S; Metoki, K.; Hommes, F. A.

doi:10.1159/000469447

“…Human ornithine transcarbamylase (OTCase) is a member of the transcarbamylase family. This group of proteins includes aspartate transcarbamylase (ATCase ; EC 2.1.3.2), OTCase (EC 2.1.3.3), oxamate transcarbamylase (EC 2.1.3.5) [1,2], putrescine transcarbamylase (EC 2.1.3.6) [3,4] and the putative lysine transcarbamylase (EC 2.1.3.8) [5,6]. These enzymes share a common biological function ; to transfer a carbamoyl group from carbamoyl phosphate (CP) to an amino group of the second substrate.…”

Section: Introductionmentioning

confidence: 99%

Human ornithine transcarbamylase: crystallographic insights into substrate recognition and conformational changes

Shi¹,

Morizono²,

Yu³

et al. 2001

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Two crystal structures of human ornithine transcarbamylase (OTCase) complexed with the substrate carbamoyl phosphate (CP) have been solved. One structure, whose crystals were prepared by substituting N-phosphonacetyl-L-ornithine (PALO) liganded crystals with CP, has been refined at 2.4 A (1 A=0.1 nm) resolution to a crystallographic R factor of 18.4%. The second structure, whose crystals were prepared by co-crystallization with CP, has been refined at 2.6 A resolution to a crystallographic R factor of 20.2%. These structures provide important new insights into substrate recognition and ligand-induced conformational changes. Comparison of these structures with the structures of OTCase complexed with the bisubstrate analogue PALO or CP and L-norvaline reveals that binding of the first substrate, CP, induces a global conformational change involving relative domain movement, whereas the binding of the second substrate brings the flexible SMG loop, which is equivalent to the 240s loop in aspartate transcarbamylase, into the active site. The model reveals structural features that define the substrate specificity of the enzyme and that regulate the order of binding and release of products.

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“…This group of proteins includes aspartate transcarbamylase (ATCase ; EC 2.1.3.2), OTCase (EC 2.1.3.3), oxamate transcarbamylase (EC 2.1.3.5) [1,2], putrescine transcarbamylase (EC 2.1.3.6) [3,4] and the putative lysine transcarbamylase (EC 2.1.3.8) [5,6]. These enzymes share a common biological function ; to transfer a carbamoyl group from carbamoyl phosphate (CP) to an amino group of the second substrate.…”

Section: Introductionmentioning

confidence: 99%

Human ornithine transcarbamylase: crystallographic insights into substrate recognition and conformational changes

Shi

¹

,

Morizono

²

,

Yu

³

et al. 2001

Biochemical Journal

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Two crystal structures of human ornithine transcarbamylase (OTCase) complexed with the substrate carbamoyl phosphate (CP) have been solved. One structure, whose crystals were prepared by substituting N-phosphonacetyl--ornithine (PALO) liganded crystals with CP, has been refined at 2.4 A / (1 A / l 0.1 nm) resolution to a crystallographic R factor of 18.4 %. The second structure, whose crystals were prepared by co-crystallization with CP, has been refined at 2.6 A / resolution to a crystallographic R factor of 20.2 %. These structures provide important new insights into substrate recognition and ligandinduced conformational changes. Comparison of these structures with the structures of OTCase complexed with the bisubstrate

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Lysine carbamoyltransferase

Springer Handbook of Enzymes

0

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Further Evidence for a Separate Enzymic Entity for the Synthesis of Homocitrulline, Distinct from the Regular Ornithine Transcarbamylase

Cited by 10 publications

References 19 publications

Human ornithine transcarbamylase: crystallographic insights into substrate recognition and conformational changes

Human ornithine transcarbamylase: crystallographic insights into substrate recognition and conformational changes

Human ornithine transcarbamylase: crystallographic insights into substrate recognition and conformational changes

Lysine carbamoyltransferase

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