Answers.Body: <p>That PDB page includes a publication reference and abstract, containing the following text:</p>
  <blockquote>
  <p>Mammalian CYP450s recognize and metabolize diverse xenobiotics such as
  drug molecules, environmental compounds and pollutants.</p>
  <p>...</p>
  <p>Here we describe the crystal structure of a human CYP450, CYP2C9, both unliganded and in complex with the anti-coagulant drug warfarin.</p>
  </blockquote>
  <p><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/?context=genome&amp;acc=GCF_000001405.38" rel="nofollow noreferrer">Here's</a> the genomic context for CYP2C9, with Ensembl page <a href="https://asia.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000138109" rel="nofollow noreferrer">here</a>.</p>
  <p>The binding pocket images from the paper <a href="https://media.springernature.com/m685/nature-assets/nature/journal/v424/n6947/images/nature01862-f1.2.jpg" rel="nofollow noreferrer">here</a> and <a href="https://media.springernature.com/m685/nature-assets/nature/journal/v424/n6947/images/nature01862-f2.2.jpg" rel="nofollow noreferrer">here</a> indicate that the following amino acids are potentially involved in the interaction:</p>
  <ul>
  <li>Arg97</li>
  <li>Phe100</li>
  <li>Ala103</li>
  <li>Val113</li>
  <li>Phe114</li>
  <li>Asn217</li>
  <li>Pro367</li>
  <li>Phe476</li>
  </ul>
  <p>Using the filtering from the <a href="https://genome.ucsc.edu/cgi-bin/hgTables" rel="nofollow noreferrer">UCSC table browser</a> (genome: Human; group: Genes &amp; Gene Predictions; Basic table; Region: genome; Identifiers: CYP2C9; Output format: CDS fasta alignment), I get the following amino acid sequences respectively for the exons in CYP2C9. I have added in the protein reference range to the end, with the help of the R <code>cumsum</code> function applied to the region lengths, <code>cumsum(c(56,54,50,54,59,47,63,47,61))</code>:</p>
  <pre><code>&gt;ENST00000260682.7_hg38_1_9 56 0 0 chr10:94938683-94938850+ [1-56]
  MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTN
  &gt;ENST00000260682.7_hg38_2_9 54 0 1 chr10:94941858-94942020+ [57-110]
  LSKVYGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGF
  &gt;ENST00000260682.7_hg38_3_9 50 1 1 chr10:94942192-94942341+ [111-160]
  GIVFSNGKKWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTK
  &gt;ENST00000260682.7_hg38_4_9 54 1 0 chr10:94947779-94947939+ [161-214]
  ASPCDPTFILGCAPCNVICSIIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQ
  &gt;ENST00000260682.7_hg38_5_9 59 0 0 chr10:94949108-94949284+ [215-273]
  ICNNFSPIIDYFPGTHNKLLKNVAFMKSYILEKVKEHQESMDMNNPQDFIDCFLMKMEK
  &gt;ENST00000260682.7_hg38_6_9 47 0 1 chr10:94972104-94972245+ [274-320]
  EKHNQPSEFTIESLENTAVDLFGAGTETTSTTLRYALLLLLKHPEVT
  &gt;ENST00000260682.7_hg38_7_9 63 1 0 chr10:94981183-94981370+ [321-383]
  AKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYIDLLPTSLPHAVTCDIKFRNYLIPK
  &gt;ENST00000260682.7_hg38_8_9 47 0 1 chr10:94986033-94986174+ [384-430]
  GTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFKKSKYFMPFSA
  &gt;ENST00000260682.7_hg38_9_9 61 1 0 chr10:94988847-94989028+ [431-491]
  GKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVPPFYQLCFIPVZ
  </code></pre>
  <p>And these nucleic acid sequences:</p>
  <pre><code>&gt;ENST00000260682.7_hg38_1_9 168 0 0 chr10:94938683-94938850+
  ATGGATTCTCTTGTGGTCCTTGTGCTCTGTCTCTCATGTTTGCTTCTCCTTTCACTCTGGAGACAGAGCTCTGGGAGAGGAAAACTCCCTCCTGGCCCCACTCCTCTCCCAGTGATTGGAAATATCCTACAGATAGGTATTAAGGACATCAGCAAATCCTTAACCAAT
  &gt;ENST00000260682.7_hg38_2_9 163 0 1 chr10:94941858-94942020+
  CTCTCAAAGGTCTATGGCCCTGTGTTCACTCTGTATTTTGGCCTGAAACCCATAGTGGTGCTGCATGGATATGAAGCAGTGAAGGAAGCCCTGATTGATCTTGGAGAGGAGTTTTCTGGAAGAGGCATTTTCCCACTGGCTGAAAGAGCTAACAGAGGATTTG
  &gt;ENST00000260682.7_hg38_3_9 150 1 1 chr10:94942192-94942341+
  GAATTGTTTTCAGCAATGGAAAGAAATGGAAGGAGATCCGGCGTTTCTCCCTCATGACGCTGCGGAATTTTGGGATGGGGAAGAGGAGCATTGAGGACCGTGTTCAAGAGGAAGCCCGCTGCCTTGTGGAGGAGTTGAGAAAAACCAAGG
  &gt;ENST00000260682.7_hg38_4_9 161 1 0 chr10:94947779-94947939+
  CCTCACCCTGTGATCCCACTTTCATCCTGGGCTGTGCTCCCTGCAATGTGATCTGCTCCATTATTTTCCATAAACGTTTTGATTATAAAGATCAGCAATTTCTTAACTTAATGGAAAAGTTGAATGAAAACATCAAGATTTTGAGCAGCCCCTGGATCCAG
  &gt;ENST00000260682.7_hg38_5_9 177 0 0 chr10:94949108-94949284+
  ATCTGCAATAATTTTTCTCCTATCATTGATTACTTCCCGGGAACTCACAACAAATTACTTAAAAACGTTGCTTTTATGAAAAGTTATATTTTGGAAAAAGTAAAAGAACACCAAGAATCAATGGACATGAACAACCCTCAGGACTTTATTGATTGCTTCCTGATGAAAATGGAGAAG
  &gt;ENST00000260682.7_hg38_6_9 142 0 1 chr10:94972104-94972245+
  GAAAAGCACAACCAACCATCTGAATTTACTATTGAAAGCTTGGAAAACACTGCAGTTGACTTGTTTGGAGCTGGGACAGAGACGACAAGCACAACCCTGAGATATGCTCTCCTTCTCCTGCTGAAGCACCCAGAGGTCACAG
  &gt;ENST00000260682.7_hg38_7_9 188 1 0 chr10:94981183-94981370+
  CTAAAGTCCAGGAAGAGATTGAACGTGTGATTGGCAGAAACCGGAGCCCCTGCATGCAAGACAGGAGCCACATGCCCTACACAGATGCTGTGGTGCACGAGGTCCAGAGATACATTGACCTTCTCCCCACCAGCCTGCCCCATGCAGTGACCTGTGACATTAAATTCAGAAACTATCTCATTCCCAAG
  &gt;ENST00000260682.7_hg38_8_9 142 0 1 chr10:94986033-94986174+
  GGCACAACCATATTAATTTCCCTGACTTCTGTGCTACATGACAACAAAGAATTTCCCAACCCAGAGATGTTTGACCCTCATCACTTTCTGGATGAAGGTGGCAATTTTAAGAAAAGTAAATACTTCATGCCTTTCTCAGCAG
  &gt;ENST00000260682.7_hg38_9_9 182 1 0 chr10:94988847-94989028+
  GAAAACGGATTTGTGTGGGAGAAGCCCTGGCCGGCATGGAGCTGTTTTTATTCCTGACCTCCATTTTACAGAACTTTAACCTGAAATCTCTGGTTGACCCAAAGAACCTTGACACCACTCCAGTTGTCAATGGATTTGCCTCTGTGCCGCCCTTCTACCAGCTGTGCTTCATTCCTGTCTGA
  </code></pre>
  <p>Associating the pocket protein amino acid numbers in exons 2,3,5,7,9 with genomic sequence using these FASTA sequences is left as an exercise for the reader.</p>
  
Answers.ContentLicense: CC BY-SA 4.0
Answers.CreationDate: 2018-09-08T21:47:07.860Z
Answers.LastActivityDate: 2018-09-08T21:47:07.860Z
Answers.LastEditDate: 2020-06-18T08:30:41.743Z
Answers.UserDisplayName: gringer
Answers.Body: <p>It turns out there is a tool that does this beautifully.  I used the <code>proteinToGenome</code> function from the <a href="https://bioconductor.org/packages/devel/bioc/vignettes/ensembldb/inst/doc/coordinate-mapping.html#5_mapping_protein_coordinates_to_the_genome" rel="nofollow noreferrer">ensembldb</a> package.</p>
  
  <p>The code looks like this:</p>
  
  <pre><code># Define the Ensemble database object for the 
  edbX &lt;- filter(EnsDb.Hsapiens.v75, filter = ~ seq_name == "X") 
  # Set the first and last amino acid you want to convert and the ensembl protein id
  GAGE10_prt &lt;- IRanges(start = 5, end = 9, names = "ENSP00000385415")
  # Perform the conversion.  GAGE10_prt is an object that has the coordinates
  GAGE10_prt &lt;- proteinToGenome(GAGE10_prt, edbX) 
  </code></pre>
  
Answers.ContentLicense: CC BY-SA 4.0
Answers.CreationDate: 2018-09-13T19:23:14.223Z
Answers.LastActivityDate: 2018-09-13T19:23:14.223Z
Answers.UserDisplayName: Greg
Body: <p>I would like to know the genomic coordinates of a proteins ligand-binding pocket.  For example, on <a href="http://www.rcsb.org/structure/1OG5" rel="nofollow noreferrer">this PDB page</a> you can see that there is xray crystallography data for how CYP2C9 interacts with two ligands. I would like to know which amino acids form the space on the protein that binds the ligands, then translate (de-translate?) that back to the nucleotide sequence. Is anyone familiar with either a database that has this information or how to extract the ligand interaction data from the PDB files?</p>
  
  <p>Thank you</p>
  
Tags: <proteins><genomics><drugs>
Title: Genomic coordinates of predicted binding pocket
ThreadText: # Genomic coordinates of predicted binding pocket
  
  (Asked by: username_0 on 2018-09-08)
  
  I would like to know the genomic coordinates of a proteins ligand-binding pocket. For example, on [this PDB page](http://www.rcsb.org/structure/1OG5) you can see that there is xray crystallography data for how CYP2C9 interacts with two ligands. I would like to know which amino acids form the space on the protein that binds the ligands, then translate (de-translate?) that back to the nucleotide sequence. Is anyone familiar with either a database that has this information or how to extract the ligand interaction data from the PDB files?
  
  Thank you
  
  **Tags:** proteins, genomics, drugs
  
  
  ---
  
  ## 2 answers
  
  ### Answer by username_0 on 2018-09-13. Score: 3 | Accepted answer
  
  It turns out there is a tool that does this beautifully. I used the `proteinToGenome` function from the [ensembldb](https://bioconductor.org/packages/devel/bioc/vignettes/ensembldb/inst/doc/coordinate-mapping.html#5_mapping_protein_coordinates_to_the_genome) package.
  
  The code looks like this:
  
  ```
  # Define the Ensemble database object for the 
  edbX <- filter(EnsDb.Hsapiens.v75, filter = ~ seq_name == "X") 
  # Set the first and last amino acid you want to convert and the ensembl protein id
  GAGE10_prt <- IRanges(start = 5, end = 9, names = "ENSP00000385415")
  # Perform the conversion.  GAGE10_prt is an object that has the coordinates
  GAGE10_prt <- proteinToGenome(GAGE10_prt, edbX) 
  
  ```
  
  
  ---
  
  ### Answer by username_1 on 2018-09-08. Score: 1
  
  That PDB page includes a publication reference and abstract, containing the following text:
  
  > Mammalian CYP450s recognize and metabolize diverse xenobiotics such as
  > drug molecules, environmental compounds and pollutants.
  >
  > ...
  >
  > Here we describe the crystal structure of a human CYP450, CYP2C9, both unliganded and in complex with the anti-coagulant drug warfarin.
  
  [Here's](https://www.ncbi.nlm.nih.gov/genome/gdv/browser/?context=genome&acc=GCF_000001405.38) the genomic context for CYP2C9, with Ensembl page [here](https://asia.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000138109).
  
  The binding pocket images from the paper [here](https://media.springernature.com/m685/nature-assets/nature/journal/v424/n6947/images/nature01862-f1.2.jpg) and [here](https://media.springernature.com/m685/nature-assets/nature/journal/v424/n6947/images/nature01862-f2.2.jpg) indicate that the following amino acids are potentially involved in the interaction:
  
  * Arg97
  * Phe100
  * Ala103
  * Val113
  * Phe114
  * Asn217
  * Pro367
  * Phe476
  
  Using the filtering from the [UCSC table browser](https://genome.ucsc.edu/cgi-bin/hgTables) (genome: Human; group: Genes & Gene Predictions; Basic table; Region: genome; Identifiers: CYP2C9; Output format: CDS fasta alignment), I get the following amino acid sequences respectively for the exons in CYP2C9. I have added in the protein reference range to the end, with the help of the R `cumsum` function applied to the region lengths, `cumsum(c(56,54,50,54,59,47,63,47,61))`:
  
  ```
  >ENST00000260682.7_hg38_1_9 56 0 0 chr10:94938683-94938850+ [1-56]
  MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTN
  >ENST00000260682.7_hg38_2_9 54 0 1 chr10:94941858-94942020+ [57-110]
  LSKVYGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGF
  >ENST00000260682.7_hg38_3_9 50 1 1 chr10:94942192-94942341+ [111-160]
  GIVFSNGKKWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTK
  >ENST00000260682.7_hg38_4_9 54 1 0 chr10:94947779-94947939+ [161-214]
  ASPCDPTFILGCAPCNVICSIIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQ
  >ENST00000260682.7_hg38_5_9 59 0 0 chr10:94949108-94949284+ [215-273]
  ICNNFSPIIDYFPGTHNKLLKNVAFMKSYILEKVKEHQESMDMNNPQDFIDCFLMKMEK
  >ENST00000260682.7_hg38_6_9 47 0 1 chr10:94972104-94972245+ [274-320]
  EKHNQPSEFTIESLENTAVDLFGAGTETTSTTLRYALLLLLKHPEVT
  >ENST00000260682.7_hg38_7_9 63 1 0 chr10:94981183-94981370+ [321-383]
  AKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYIDLLPTSLPHAVTCDIKFRNYLIPK
  >ENST00000260682.7_hg38_8_9 47 0 1 chr10:94986033-94986174+ [384-430]
  GTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFKKSKYFMPFSA
  >ENST00000260682.7_hg38_9_9 61 1 0 chr10:94988847-94989028+ [431-491]
  GKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVPPFYQLCFIPVZ
  
  ```
  
  And these nucleic acid sequences:
  
  ```
  >ENST00000260682.7_hg38_1_9 168 0 0 chr10:94938683-94938850+
  ATGGATTCTCTTGTGGTCCTTGTGCTCTGTCTCTCATGTTTGCTTCTCCTTTCACTCTGGAGACAGAGCTCTGGGAGAGGAAAACTCCCTCCTGGCCCCACTCCTCTCCCAGTGATTGGAAATATCCTACAGATAGGTATTAAGGACATCAGCAAATCCTTAACCAAT
  >ENST00000260682.7_hg38_2_9 163 0 1 chr10:94941858-94942020+
  CTCTCAAAGGTCTATGGCCCTGTGTTCACTCTGTATTTTGGCCTGAAACCCATAGTGGTGCTGCATGGATATGAAGCAGTGAAGGAAGCCCTGATTGATCTTGGAGAGGAGTTTTCTGGAAGAGGCATTTTCCCACTGGCTGAAAGAGCTAACAGAGGATTTG
  >ENST00000260682.7_hg38_3_9 150 1 1 chr10:94942192-94942341+
  GAATTGTTTTCAGCAATGGAAAGAAATGGAAGGAGATCCGGCGTTTCTCCCTCATGACGCTGCGGAATTTTGGGATGGGGAAGAGGAGCATTGAGGACCGTGTTCAAGAGGAAGCCCGCTGCCTTGTGGAGGAGTTGAGAAAAACCAAGG
  >ENST00000260682.7_hg38_4_9 161 1 0 chr10:94947779-94947939+
  CCTCACCCTGTGATCCCACTTTCATCCTGGGCTGTGCTCCCTGCAATGTGATCTGCTCCATTATTTTCCATAAACGTTTTGATTATAAAGATCAGCAATTTCTTAACTTAATGGAAAAGTTGAATGAAAACATCAAGATTTTGAGCAGCCCCTGGATCCAG
  >ENST00000260682.7_hg38_5_9 177 0 0 chr10:94949108-94949284+
  ATCTGCAATAATTTTTCTCCTATCATTGATTACTTCCCGGGAACTCACAACAAATTACTTAAAAACGTTGCTTTTATGAAAAGTTATATTTTGGAAAAAGTAAAAGAACACCAAGAATCAATGGACATGAACAACCCTCAGGACTTTATTGATTGCTTCCTGATGAAAATGGAGAAG
  >ENST00000260682.7_hg38_6_9 142 0 1 chr10:94972104-94972245+
  GAAAAGCACAACCAACCATCTGAATTTACTATTGAAAGCTTGGAAAACACTGCAGTTGACTTGTTTGGAGCTGGGACAGAGACGACAAGCACAACCCTGAGATATGCTCTCCTTCTCCTGCTGAAGCACCCAGAGGTCACAG
  >ENST00000260682.7_hg38_7_9 188 1 0 chr10:94981183-94981370+
  CTAAAGTCCAGGAAGAGATTGAACGTGTGATTGGCAGAAACCGGAGCCCCTGCATGCAAGACAGGAGCCACATGCCCTACACAGATGCTGTGGTGCACGAGGTCCAGAGATACATTGACCTTCTCCCCACCAGCCTGCCCCATGCAGTGACCTGTGACATTAAATTCAGAAACTATCTCATTCCCAAG
  >ENST00000260682.7_hg38_8_9 142 0 1 chr10:94986033-94986174+
  GGCACAACCATATTAATTTCCCTGACTTCTGTGCTACATGACAACAAAGAATTTCCCAACCCAGAGATGTTTGACCCTCATCACTTTCTGGATGAAGGTGGCAATTTTAAGAAAAGTAAATACTTCATGCCTTTCTCAGCAG
  >ENST00000260682.7_hg38_9_9 182 1 0 chr10:94988847-94989028+
  GAAAACGGATTTGTGTGGGAGAAGCCCTGGCCGGCATGGAGCTGTTTTTATTCCTGACCTCCATTTTACAGAACTTTAACCTGAAATCTCTGGTTGACCCAAAGAACCTTGACACCACTCCAGTTGTCAATGGATTTGCCTCTGTGCCGCCCTTCTACCAGCTGTGCTTCATTCCTGTCTGA
  
  ```
  
  Associating the pocket protein amino acid numbers in exons 2,3,5,7,9 with genomic sequence using these FASTA sequences is left as an exercise for the reader.
  
  
  ---
  
  