Sandbox Reserved 328: Difference between revisions
From Proteopedia
Jump to navigationJump to search
Simon Loewen (talk | contribs) No edit summary |
Simon Loewen (talk | contribs) No edit summary |
||
| Line 8: | Line 8: | ||
==Overall Structure== | ==Overall Structure== | ||
HisD is a homodimer, with each subunit consisting of a globule segment, and an extending tail. The two larger domains (1 and 2) are within the globule, and domains 3 and 4 are found in the tail. The cores of both domains (residues 124–236 in domain 1 & 237–381 in domain 2) adopt incomplete Rossmann folds, which lack the last strand-helix hairpin<ref name="1kar" />. To carry out its function, HisD relies on the presence of one Zn2+ cation per monomer, not for catalysis, but for substrate binding. The Zn2+ cation is located at the bottom of the cavity occupied by the substrate and is octahedrally coordinated by four seperate residues. Along with Zn, the coordination of the substrate in the active site is assisted by the large degree of secondary structure present in the protein. The substrate binds in a deep pocket formed at the dimer interface between domains 1, 2, and 4, with most interactions being with residues at the N-terminal end of the β-sheet found within domain 2. Large amounts of secondary structure both in the form of <scene name='Sandbox_Reserved_328/Helices/1'>alpha helices</scene> and <scene name='Sandbox_Reserved_328/Beta_sheets/1'>beta sheets</scene> are present, and serve to provide a base for the overall structure of the molecule. | HisD is a homodimer, with each subunit consisting of a globule segment, and an extending tail. The two larger domains (1 and 2) are within the globule, and domains 3 and 4 are found in the tail. The cores of both domains (residues 124–236 in domain 1 & 237–381 in domain 2) adopt incomplete Rossmann folds, which lack the last strand-helix hairpin<ref name="1kar" />. To carry out its function, HisD relies on the presence of one Zn2+ cation per monomer, not for catalysis, but for substrate binding. The Zn2+ cation is located at the bottom of the cavity occupied by the substrate and is octahedrally coordinated by four seperate residues. Along with Zn, the coordination of the substrate in the active site is assisted by the large degree of secondary structure present in the protein. The substrate binds in a deep pocket formed at the dimer interface between domains 1, 2, and 4, with most interactions being with residues at the N-terminal end of the β-sheet found within domain 2. Large amounts of secondary structure both in the form of <scene name='Sandbox_Reserved_328/Helices/1'>alpha helices</scene> and <scene name='Sandbox_Reserved_328/Beta_sheets/1'>beta sheets</scene> are present, and serve to provide a base for the overall structure of the molecule. | ||
Crystallogaphic data of HisD bound with NAD+ shows that the structure that allows the binding resembles to some extent the mode of binding observed in the aldehyde dehydrogenases, which have a six-residue insertion in the P loop. Overall, the method of binding differs from this class in that the insertions are usualy shorter, and translated approximately 10Å. | |||
==Enzymatic mechanism== | ==Enzymatic mechanism== | ||
