Sonic Hedgehog: Difference between revisions

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[[Image:Catalytic site.png |left| thumb | '''Figure 1.''' A close-up of the zinc coordination site of Shh-N, showing His 141, Asp 148, and His 183 separated by distances of 2.06, 1.97, and 2.08 Å, respectively. The zinc-bound water molecule is also shown in line with Glu 177, which is thought to participate in hydrolysis by abstracting a proton from the water molecule<ref name="Palm"/>.]] The three-dimensional structure of murine Shh-N (residues 39-195) is shown as 1VHH. An α + β sandwich consisting of two <scene name='Sandbox_191/Scene2/5'> α-helices</scene> and a six-stranded, mixed <scene name='Sandbox_191/Scene3/5'> β-sheet</scene> makes up the core of the structure, along with a two-stranded, antiparallel β-sheet<ref name="Palm"/>. Although this type of folding arrangement has not yet been seen in other proteins, the presence of a <scene name='Sandbox_191/Scene4/3'>tetrahedrally coordinated zinc ion</scene> in Shh-N bears close structural resemblance to the zinc coordination sites of zinc hydrolases, including thermolysin and carboxypeptidase A. Three amino acid side chains – <scene name='Sandbox_191/Scene4/4'>His 141, Asp 148, and His 183</scene> – are bound to the zinc ion in the crystal structure, along with a single <scene name='Sandbox_191/Scene4/5'>molecule of water</scene> (Figure 1). Zinc ions that serve a structural role in proteins are normally coordinated by four amino acid side chains and are not usually exposed to the surrounding solvent. The presence of a zinc-bound water molecule in Shh-N, by contrast, is indicative of a catalytic function. In zinc hydrolases, the water molecule is key to the protein's enzymatic activity when its proton is removed by a nearby glutamate residue. <scene name='Sandbox_191/Scene4/6'>Glu 177</scene> (Figure 1) likely serves the same role in Shh-N, further supporting a novel, hydrolytic function for this protein. Based on the catalytic mechanisms for thermolysin and carboxypeptidase A, three non-coordinating residues in Shh-N (<scene name='Sandbox_191/Scene4/7'>His 135, His 181, and Glu 127</scene>) are also believed to participate in a potential hydrolysis reaction<ref name="Palm">PMID: 7477329</ref>.

The crystal structure of Shh-N contains a single sulphate molecule.

The crystal structure of Shh-N also contains a single sulphate molecule, which interacts with arginine residues at the interface of two Shh-N molecules. Since Shh-N binds heparin, this interaction is believed to comprise a heparin-binding region<ref name="palm"/>.

= Function =

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@@ Line 15: / Line 15: @@
 [[Image:Catalytic site.png |left| thumb | '''Figure 1.''' A close-up of the zinc coordination site of Shh-N, showing His 141, Asp 148, and His 183 separated by distances of 2.06, 1.97, and 2.08 Å, respectively. The zinc-bound water molecule is also shown in line with Glu 177, which is thought to participate in hydrolysis by abstracting a proton from the water molecule<ref name="Palm"/>.]] The three-dimensional structure of murine Shh-N (residues 39-195) is shown as 1VHH. An α + β sandwich consisting of two <scene name='Sandbox_191/Scene2/5'> α-helices</scene> and a six-stranded, mixed <scene name='Sandbox_191/Scene3/5'> β-sheet</scene> makes up the core of the structure, along with a two-stranded, antiparallel β-sheet<ref name="Palm"/>. Although this type of folding arrangement has not yet been seen in other proteins, the presence of a <scene name='Sandbox_191/Scene4/3'>tetrahedrally coordinated zinc ion</scene> in Shh-N bears close structural resemblance to the zinc coordination sites of zinc hydrolases, including thermolysin and carboxypeptidase A. Three amino acid side chains – <scene name='Sandbox_191/Scene4/4'>His 141, Asp 148, and His 183</scene> – are bound to the zinc ion in the crystal structure, along with a single <scene name='Sandbox_191/Scene4/5'>molecule of water</scene> (Figure 1). Zinc ions that serve a structural role in proteins are normally coordinated by four amino acid side chains and are not usually exposed to the surrounding solvent. The presence of a zinc-bound water molecule in Shh-N, by contrast, is indicative of a catalytic function. In zinc hydrolases, the water molecule is key to the protein's enzymatic activity when its proton is removed by a nearby glutamate residue. <scene name='Sandbox_191/Scene4/6'>Glu 177</scene> (Figure 1) likely serves the same role in Shh-N, further supporting a novel, hydrolytic function for this protein. Based on the catalytic mechanisms for thermolysin and carboxypeptidase A, three non-coordinating residues in Shh-N (<scene name='Sandbox_191/Scene4/7'>His 135, His 181, and Glu 127</scene>) are also believed to participate in a potential hydrolysis reaction<ref name="Palm">PMID: 7477329</ref>.
-The crystal structure of Shh-N contains a single sulphate molecule.
+The crystal structure of Shh-N also contains a single sulphate molecule, which interacts with arginine residues at the interface of two Shh-N molecules. Since Shh-N binds heparin, this interaction is believed to comprise a heparin-binding region<ref name="palm"/>.
 = Function =