1EP9

HUMAN ORNITHINE TRANSCARBAMYLASE: CRYSTALLOGRAPHIC INSIGHTS INTO SUBSTRATE RECOGNITION AND CONFORMATIONAL CHANGE

Summary for 1EP9

• Entry DOI: 10.2210/pdb1ep9/pdb
• Related: 1OTH 1c9Y
• Descriptor: ORNITHINE TRANSCARBAMYLASE, PHOSPHORIC ACID MONO(FORMAMIDE)ESTER (3 entities in total)
• Functional Keywords: protein-substrate complex, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion matrix: P00480
• Total number of polymer chains: 1
• Total formula weight: 36247.57

Authors

Shi, D.,Morizono, H.,Yu, X.,Allewell, N.M.,Tuchman, M. (deposition date: 2000-03-28, release date: 2001-04-04, Last modification date: 2024-05-22)

Primary citation

Shi, D.,Morizono, H.,Yu, X.,Tong, L.,Allewell, N.M.,Tuchman, M.
Human ornithine transcarbamylase: crystallographic insights into substrate recognition and conformational changes.
Biochem.J., 354:501-509, 2001

PubMed Abstract: 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.

PubMed: 11237854
DOI: 10.1042/0264-6021:3540501

Experimental method

X-RAY DIFFRACTION (2.4 Å)