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4yvf

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Revision as of 07:28, 10 May 2023

Structure of S-adenosyl-L-homocysteine hydrolase

Structural highlights

4yvf is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SAHH_HUMAN Defects in AHCY are the cause of hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency (HMAHCHD) [MIM:613752. A metabolic disorder characterized by hypermethioninemia associated with failure to thrive, mental and motor retardation, facial dysmorphism with abnormal hair and teeth, and myocardiopathy.^[1] ^[2] ^[3] ^[4]

Function

SAHH_HUMAN Adenosylhomocysteine is a competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine.^[5]

Publication Abstract from PubMed

Optimization of a new series of S-adenosyl-L-homocysteine hydrolase (AdoHcyase) inhibitors based on non-adenosine analogs led to very potent compounds 14n, 18a, and 18b with IC50 values of 13 +/- 3, 5.0 +/- 2.0, and 8.5 +/- 3.1 nM, respectively. An X-ray crystal structure of AdoHcyase with NAD(+) and 18a showed a novel open form co-crystal structure. 18a in the co-crystals formed intramolecular eight membered ring hydrogen bond formations. A single crystal X-ray structure of 14n also showed an intramolecular eight-membered ring hydrogen bond interaction.

Discovery and structural analyses of S-adenosyl-L-homocysteine hydrolase inhibitors based on non-adenosine analogs.,Nakao A, Suzuki H, Ueno H, Iwasaki H, Setsuta T, Kashima A, Sunada S Bioorg Med Chem. 2015 Aug 1;23(15):4952-69. doi: 10.1016/j.bmc.2015.05.018. Epub , 2015 May 19. PMID:26037610^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Baric I, Fumic K, Glenn B, Cuk M, Schulze A, Finkelstein JD, James SJ, Mejaski-Bosnjak V, Pazanin L, Pogribny IP, Rados M, Sarnavka V, Scukanec-Spoljar M, Allen RH, Stabler S, Uzelac L, Vugrek O, Wagner C, Zeisel S, Mudd SH. S-adenosylhomocysteine hydrolase deficiency in a human: a genetic disorder of methionine metabolism. Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4234-9. Epub 2004 Mar 15. PMID:15024124 doi:10.1073/pnas.0400658101
↑ Buist NR, Glenn B, Vugrek O, Wagner C, Stabler S, Allen RH, Pogribny I, Schulze A, Zeisel SH, Baric I, Mudd SH. S-adenosylhomocysteine hydrolase deficiency in a 26-year-old man. J Inherit Metab Dis. 2006 Aug;29(4):538-45. Epub 2006 May 30. PMID:16736098 doi:10.1007/s10545-006-0240-0
↑ Vugrek O, Beluzic R, Nakic N, Mudd SH. S-adenosylhomocysteine hydrolase (AHCY) deficiency: two novel mutations with lethal outcome. Hum Mutat. 2009 Apr;30(4):E555-65. doi: 10.1002/humu.20985. PMID:19177456 doi:10.1002/humu.20985
↑ Grubbs R, Vugrek O, Deisch J, Wagner C, Stabler S, Allen R, Baric I, Rados M, Mudd SH. S-adenosylhomocysteine hydrolase deficiency: two siblings with fetal hydrops and fatal outcomes. J Inherit Metab Dis. 2010 Dec;33(6):705-13. doi: 10.1007/s10545-010-9171-x. Epub , 2010 Sep 18. PMID:20852937 doi:10.1007/s10545-010-9171-x
↑ Yang X, Hu Y, Yin DH, Turner MA, Wang M, Borchardt RT, Howell PL, Kuczera K, Schowen RL. Catalytic strategy of S-adenosyl-L-homocysteine hydrolase: transition-state stabilization and the avoidance of abortive reactions. Biochemistry. 2003 Feb 25;42(7):1900-9. PMID:12590576 doi:http://dx.doi.org/10.1021/bi0262350
↑ Nakao A, Suzuki H, Ueno H, Iwasaki H, Setsuta T, Kashima A, Sunada S. Discovery and structural analyses of S-adenosyl-L-homocysteine hydrolase inhibitors based on non-adenosine analogs. Bioorg Med Chem. 2015 Aug 1;23(15):4952-69. doi: 10.1016/j.bmc.2015.05.018. Epub , 2015 May 19. PMID:26037610 doi:http://dx.doi.org/10.1016/j.bmc.2015.05.018

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4yvf"

Categories: Homo sapiens | Large Structures | Akiko K

@@ Line 3: / Line 3: @@
 <StructureSection load='4yvf' size='340' side='right'caption='[[4yvf]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4yvf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YVF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YVF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4yvf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YVF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YVF FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=XFA:2-{[5-CHLORO-2-(4-CHLOROPHENOXY)PHENYL](2-{[2-(METHYLAMINO)ETHYL]AMINO}-2-OXOETHYL)AMINO}-N-(1,3-DIHYDRO-2H-ISOINDOL-2-YL)-N-METHYLACETAMIDE'>XFA</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=XFA:2-{[5-CHLORO-2-(4-CHLOROPHENOXY)PHENYL](2-{[2-(METHYLAMINO)ETHYL]AMINO}-2-OXOETHYL)AMINO}-N-(1,3-DIHYDRO-2H-ISOINDOL-2-YL)-N-METHYLACETAMIDE'>XFA</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AHCY, SAHH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4yvf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yvf OCA], [https://pdbe.org/4yvf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yvf RCSB], [https://www.ebi.ac.uk/pdbsum/4yvf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yvf ProSAT]</span></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenosylhomocysteinase Adenosylhomocysteinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.1.1 3.3.1.1] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yvf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yvf OCA], [http://pdbe.org/4yvf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yvf RCSB], [http://www.ebi.ac.uk/pdbsum/4yvf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yvf ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/SAHH_HUMAN SAHH_HUMAN]] Defects in AHCY are the cause of hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency (HMAHCHD) [MIM:[http://omim.org/entry/613752 613752]]. A metabolic disorder characterized by hypermethioninemia associated with failure to thrive, mental and motor retardation, facial dysmorphism with abnormal hair and teeth, and myocardiopathy.<ref>PMID:15024124</ref> <ref>PMID:16736098</ref> <ref>PMID:19177456</ref> <ref>PMID:20852937</ref>
+[https://www.uniprot.org/uniprot/SAHH_HUMAN SAHH_HUMAN] Defects in AHCY are the cause of hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency (HMAHCHD) [MIM:[https://omim.org/entry/613752 613752]. A metabolic disorder characterized by hypermethioninemia associated with failure to thrive, mental and motor retardation, facial dysmorphism with abnormal hair and teeth, and myocardiopathy.<ref>PMID:15024124</ref> <ref>PMID:16736098</ref> <ref>PMID:19177456</ref> <ref>PMID:20852937</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/SAHH_HUMAN SAHH_HUMAN]] Adenosylhomocysteine is a competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine.<ref>PMID:12590576</ref>
+[https://www.uniprot.org/uniprot/SAHH_HUMAN SAHH_HUMAN] Adenosylhomocysteine is a competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine.<ref>PMID:12590576</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Adenosylhomocysteinase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Akiko, K]]
+[[Category: Akiko K]]
-[[Category: Hydrolase]]
-[[Category: Sahh]]

4yvf

From Proteopedia

Revision as of 07:28, 10 May 2023

Structure of S-adenosyl-L-homocysteine hydrolase

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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