Sandbox WWC2: Difference between revisions

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== Structure ==

Unlike its related dimers, human MAO-B and rat MAO-A, human MAO-A is a monomer composed of 527 amino acids, with a molecular weight of 60,512±6 Da. The first 497 amino acids in the polypeptide exist in the cytoplasm of the cell; while amino acids 498—518 are involved in an α-helix that anchors the enzyme to the mitochondrial membrane (this can clearly be seen in the provided crystal structure as the only α-helix that significantly sticks out away from the rest of the globular structure). Furthermore, amino acids 519—527 are present in the intermembrane of the mitochondria [http://www.uniprot.org/uniprot/P2139]. The active site of MAO-A is a single hydrophobic pocket with a volume of approximately 550 cubic Å [http://www.pnas.org/content/102/36/12684.full]. Moreover, the active site of human MAO-A is completely unique due to a loop-like conformation of residues 210-216, ~~which~~ is thought to be the result of interactions taking place across the monomer, which allow for the development of inhibitors specific to human MAO-A [http://www.ncbi.nlm.nih.gov/pubmed/16129825].

Unlike its related dimers, human MAO-B and rat MAO-A, human MAO-A is a monomer composed of 527 amino acids, with a molecular weight of 60,512±6 Da. The first 497 amino acids in the polypeptide exist in the cytoplasm of the cell; while amino acids 498—518 are involved in an α-helix that anchors the enzyme to the mitochondrial membrane (this can clearly be seen in the provided crystal structure as the only α-helix that significantly sticks out away from the rest of the globular structure). Furthermore, amino acids 519—527 are present in the intermembrane of the mitochondria [http://www.uniprot.org/uniprot/P2139]. The active site of MAO-A is a single hydrophobic pocket, lined with 11 aliphatic and 5 aromatic residues, with a volume of approximately 550 cubic Å [http://www.pnas.org/content/102/36/12684.full]. Moreover, the active site of human MAO-A is completely unique due to a loop-like conformation of residues 210-216, this is thought to be the result of interactions taking place across the monomer, which allow for the development of inhibitors specific to human MAO-A [http://www.ncbi.nlm.nih.gov/pubmed/16129825]. There are two crucial differences in the active sites of human MAO-A and -B, these include residues Phe-208 (Ile-199 in human MAO B) and Ile-335 (Tyr-326 in human hMAO B) [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200291/].

The enzyme shares 70% of its amino acid sequence with human MAO-B, and the amino acids interacting with the FAD binding site in both isoforms is conserved,; therefore it is believed that the FAD binding sites are quite similar in both proteins [http://www.ncbi.nlm.nih.gov/pubmed/14697881]. Bach et al (1988) showed that the FAD is covalently bound to cysteine residues in both human MAO-A and -B, on Cys397 and Cys406, respectively [http://thirdworld.nl/the-fad-binding-sites-of-human-monoamine-oxidases-a-and-b].

Sandbox WWC2: Difference between revisions

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 == Structure ==
-Unlike its related dimers, human MAO-B and rat MAO-A, human MAO-A is a monomer composed of 527 amino acids, with a molecular weight of 60,512±6 Da. The first 497 amino acids in the polypeptide exist in the cytoplasm of the cell; while amino acids 498—518 are involved in an α-helix that anchors the enzyme to the mitochondrial membrane (this can clearly be seen in the provided crystal structure as the only α-helix that significantly sticks out away from the rest of the globular structure). Furthermore, amino acids 519—527 are present in the intermembrane of the mitochondria [http://www.uniprot.org/uniprot/P2139]. The active site of MAO-A is a single hydrophobic pocket with a volume of approximately 550 cubic Å [http://www.pnas.org/content/102/36/12684.full]. Moreover, the active site of human MAO-A is completely unique due to a loop-like conformation of residues 210-216, which is thought to be the result of interactions taking place across the monomer, which allow for the development of inhibitors specific to human MAO-A [http://www.ncbi.nlm.nih.gov/pubmed/16129825].
+Unlike its related dimers, human MAO-B and rat MAO-A, human MAO-A is a monomer composed of 527 amino acids, with a molecular weight of 60,512±6 Da. The first 497 amino acids in the polypeptide exist in the cytoplasm of the cell; while amino acids 498—518 are involved in an α-helix that anchors the enzyme to the mitochondrial membrane (this can clearly be seen in the provided crystal structure as the only α-helix that significantly sticks out away from the rest of the globular structure). Furthermore, amino acids 519—527 are present in the intermembrane of the mitochondria [http://www.uniprot.org/uniprot/P2139]. The active site of MAO-A is a single hydrophobic pocket, lined with 11 aliphatic and 5 aromatic residues, with a volume of approximately 550 cubic Å [http://www.pnas.org/content/102/36/12684.full]. Moreover, the active site of human MAO-A is completely unique due to a loop-like conformation of residues 210-216, this is thought to be the result of interactions taking place across the monomer, which allow for the development of inhibitors specific to human MAO-A [http://www.ncbi.nlm.nih.gov/pubmed/16129825]. There are two crucial differences in the active sites of human MAO-A and -B, these include residues Phe-208 (Ile-199 in human MAO B) and Ile-335 (Tyr-326 in human hMAO B) [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200291/].
 The enzyme shares 70% of its amino acid sequence with human MAO-B, and the amino acids interacting with the FAD binding site in both isoforms is conserved,; therefore it is believed that the FAD binding sites are quite similar in both proteins [http://www.ncbi.nlm.nih.gov/pubmed/14697881]. Bach et al (1988) showed that the FAD is covalently bound to cysteine residues in both human MAO-A and -B, on Cys397 and Cys406, respectively [http://thirdworld.nl/the-fad-binding-sites-of-human-monoamine-oxidases-a-and-b].