3vbv - Revision history

OCA at 10:35, 1 March 2024

2024-03-01T10:35:02Z

← Older revision		Revision as of 10:35, 1 March 2024
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	<StructureSection load='3vbv' size='340' side='right'caption='[[3vbv]], [[Resolution\|resolution]] 2.08Å' scene=''>		<StructureSection load='3vbv' size='340' side='right'caption='[[3vbv]], [[Resolution\|resolution]] 2.08Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3vbv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VBV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VBV FirstGlance]. <br>		<table><tr><td colspan='2'>[[3vbv]] is a 1 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=3VBV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VBV FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=0FK:8~~-~~HYDROXYQUINOLINE-2-CARBOXAMIDE'>0FK</scene></td></tr>~~		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.08Å</td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>~~[[~~Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em~~;~~'>[[3vbq\|3vbq]], [[3vbt\|3vbt]], [[3vbw\|3vbw]], [[3vbx\|3vbx]], [[3vby\|3vby]], [[3vc4\|3vc4]]</div>~~</td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0FK:8-HYDROXYQUINOLINE-2-CARBOXAMIDE'>0FK</scene></td></tr>
	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>PIM1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=9606 HUMAN])</td></tr>~~
	~~<tr id='activity'><td class~~="~~sblockLbl~~"><~~b>Activity:</b></td><td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[https~~:~~//en.wikipedia.org/wiki/Non~~-~~specific_serine/threonine_protein_kinase Non~~-~~specific serine/threonine protein kinase], with EC number [https://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1]~~ </~~span~~></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=3vbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vbv OCA], [https://pdbe.org/3vbv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vbv RCSB], [https://www.ebi.ac.uk/pdbsum/3vbv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vbv ProSAT]</span></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=3vbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vbv OCA], [https://pdbe.org/3vbv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vbv RCSB], [https://www.ebi.ac.uk/pdbsum/3vbv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vbv ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/PIM1_HUMAN PIM1_HUMAN]] Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.<ref>PMID:1825810</ref> <ref>PMID:10664448</ref> <ref>PMID:12431783</ref> <ref>PMID:15528381</ref> <ref>PMID:16356754</ref> <ref>PMID:18593906</ref> <ref>PMID:19749799</ref>		[https://www.uniprot.org/uniprot/PIM1_HUMAN PIM1_HUMAN] Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.<ref>PMID:1825810</ref> <ref>PMID:10664448</ref> <ref>PMID:12431783</ref> <ref>PMID:15528381</ref> <ref>PMID:16356754</ref> <ref>PMID:18593906</ref> <ref>PMID:19749799</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	We have studied the subtleties of fragment docking and binding using data generated in a Pim-1 kinase inhibitor program. Crystallographic and docking data analyses have been undertaken using inhibitor complexes derived from an in-house surface plasmon resonance (SPR) fragment screen, a virtual needle screen, and a de novo designed fragment inhibitor hybrid. These investigations highlight that fragments that do not fill their binding pocket can exhibit promiscuous hydrophobic interactions due to the lack of steric constraints imposed on them by the boundaries of said pocket. As a result, docking modes that disagree with an observed crystal structure but maintain key crystallographically observed hydrogen bonds still have potential value in ligand design and optimization. This observation runs counter to the lore in fragment-based drug design that all fragment elaboration must be based on the parent crystal structure alone.

	Implications of Promiscuous Pim-1 Kinase Fragment Inhibitor Hydrophobic Interactions for Fragment-Based Drug Design.,Good AC, Liu J, Hirth B, Asmussen G, Xiang Y, Biemann HP, Bishop KA, Fremgen T, Fitzgerald M, Gladysheva T, Jain A, Jancsics K, Metz M, Papoulis A, Skerlj R, Stepp JD, Wei RR J Med Chem. 2012 Mar 5. PMID:22339127<ref>PMID:22339127</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 3vbv" style="background-color:#fffaf0;"></div~~>

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Non-specific serine/threonine protein kinase]]~~		[[Category: Liu J]]
	[[Category: Liu, J]]
	~~[[Category: Pim1]]~~
	~~[[Category: Transferase-transferase inhibitor complex~~]]

OCA at 18:37, 27 July 2022

2022-07-27T18:37:29Z

← Older revision		Revision as of 18:37, 27 July 2022
Line 1:		Line 1:

	==Exploitation of hydrogen bonding constraints and flat hydrophobic energy landscapes in Pim-1 kinase needle screening and inhibitor design==		==Exploitation of hydrogen bonding constraints and flat hydrophobic energy landscapes in Pim-1 kinase needle screening and inhibitor design==
	<StructureSection load='3vbv' size='340' side='right' caption='[[3vbv]], [[Resolution\|resolution]] 2.08Å' scene=''>		<StructureSection load='3vbv' size='340' side='right'caption='[[3vbv]], [[Resolution\|resolution]] 2.08Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3vbv]] is a 1 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=3VBV OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3VBV FirstGlance]. <br>		<table><tr><td colspan='2'>[[3vbv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VBV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VBV FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0FK:8-HYDROXYQUINOLINE-2-CARBOXAMIDE'>0FK</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0FK:8-HYDROXYQUINOLINE-2-CARBOXAMIDE'>0FK</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vbq\|3vbq]], [[3vbt\|3vbt]], [[3vbw\|3vbw]], [[3vbx\|3vbx]], [[3vby\|3vby]], [[3vc4\|3vc4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3vbq\|3vbq]], [[3vbt\|3vbt]], [[3vbw\|3vbw]], [[3vbx\|3vbx]], [[3vby\|3vby]], [[3vc4\|3vc4]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIM1 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIM1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3vbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vbv OCA], [~~http~~://pdbe.org/3vbv PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3vbv RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3vbv PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3vbv ProSAT]</span></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=3vbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vbv OCA], [https://pdbe.org/3vbv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vbv RCSB], [https://www.ebi.ac.uk/pdbsum/3vbv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vbv ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/PIM1_HUMAN PIM1_HUMAN]] Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.<ref>PMID:1825810</ref> <ref>PMID:10664448</ref> <ref>PMID:12431783</ref> <ref>PMID:15528381</ref> <ref>PMID:16356754</ref> <ref>PMID:18593906</ref> <ref>PMID:19749799</ref>		[[https://www.uniprot.org/uniprot/PIM1_HUMAN PIM1_HUMAN]] Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.<ref>PMID:1825810</ref> <ref>PMID:10664448</ref> <ref>PMID:12431783</ref> <ref>PMID:15528381</ref> <ref>PMID:16356754</ref> <ref>PMID:18593906</ref> <ref>PMID:19749799</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 23:

	==See Also==		==See Also==
	*[[~~Proto-oncogene serine~~/threonine-protein kinase\|~~Proto-oncogene serine~~/threonine-protein kinase]]		*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
			*[[3D structures of pim-1\|3D structures of pim-1]]
	== References ==		== References ==
	<references/>		<references/>
Line 29:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Liu, J]]		[[Category: Liu, J]]
	[[Category: Pim1]]		[[Category: Pim1]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 19:17, 5 August 2016

2016-08-05T19:17:54Z

← Older revision		Revision as of 19:17, 5 August 2016
Line 1:		Line 1:

	==Exploitation of hydrogen bonding constraints and flat hydrophobic energy landscapes in Pim-1 kinase needle screening and inhibitor design==		==Exploitation of hydrogen bonding constraints and flat hydrophobic energy landscapes in Pim-1 kinase needle screening and inhibitor design==
	<StructureSection load='3vbv' size='340' side='right' caption='[[3vbv]], [[Resolution\|resolution]] 2.08Å' scene=''>		<StructureSection load='3vbv' size='340' side='right' caption='[[3vbv]], [[Resolution\|resolution]] 2.08Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3vbv]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VBV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VBV FirstGlance]. <br>		<table><tr><td colspan='2'>[[3vbv]] is a 1 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=3VBV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VBV FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0FK:8-HYDROXYQUINOLINE-2-CARBOXAMIDE'>0FK</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0FK:8-HYDROXYQUINOLINE-2-CARBOXAMIDE'>0FK</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vbq\|3vbq]], [[3vbt\|3vbt]], [[3vbw\|3vbw]], [[3vbx\|3vbx]], [[3vby\|3vby]], [[3vc4\|3vc4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vbq\|3vbq]], [[3vbt\|3vbt]], [[3vbw\|3vbw]], [[3vbx\|3vbx]], [[3vby\|3vby]], [[3vc4\|3vc4]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3vbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vbv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vbv RCSB], [http://www.ebi.ac.uk/pdbsum/3vbv PDBsum]</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=3vbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vbv OCA], [http://pdbe.org/3vbv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vbv RCSB], [http://www.ebi.ac.uk/pdbsum/3vbv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vbv ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 3vbv" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Liu, J]]		[[Category: Liu, J]]
	[[Category: Pim1]]		[[Category: Pim1]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 05:09, 25 December 2014

2014-12-25T05:09:16Z

← Older revision		Revision as of 05:09, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3vbv]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VBV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VBV FirstGlance]. <br>		<table><tr><td colspan='2'>[[3vbv]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VBV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VBV FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0FK:8-HYDROXYQUINOLINE-2-CARBOXAMIDE'>0FK</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0FK:8-HYDROXYQUINOLINE-2-CARBOXAMIDE'>0FK</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vbq\|3vbq]], [[3vbt\|3vbt]], [[3vbw\|3vbw]], [[3vbx\|3vbx]], [[3vby\|3vby]], [[3vc4\|3vc4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vbq\|3vbq]], [[3vbt\|3vbt]], [[3vbw\|3vbw]], [[3vbx\|3vbx]], [[3vby\|3vby]], [[3vc4\|3vc4]]</td></tr>
	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vbv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vbv RCSB], [http://www.ebi.ac.uk/pdbsum/3vbv PDBsum]</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=3vbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vbv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vbv RCSB], [http://www.ebi.ac.uk/pdbsum/3vbv PDBsum]</span></td></tr>
	<table>		</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/PIM1_HUMAN PIM1_HUMAN]] Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.<ref>PMID:1825810</ref> <ref>PMID:10664448</ref> <ref>PMID:12431783</ref> <ref>PMID:15528381</ref> <ref>PMID:16356754</ref> <ref>PMID:18593906</ref> <ref>PMID:19749799</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 28:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Liu, J.]]		[[Category: Liu, J]]
	[[Category: Pim1]]		[[Category: Pim1]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 08:25, 5 June 2014

2014-06-05T08:25:35Z

← Older revision		Revision as of 08:25, 5 June 2014
Line 1:		Line 1:
	[[~~Image~~:~~3vbv~~.~~png~~\|~~left~~\|~~200px~~]]		==Exploitation of hydrogen bonding constraints and flat hydrophobic energy landscapes in Pim-1 kinase needle screening and inhibitor design==
			<StructureSection load='3vbv' size='340' side='right' caption='[[3vbv]], [[Resolution\|resolution]] 2.08Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[3vbv]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VBV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VBV FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0FK:8-HYDROXYQUINOLINE-2-CARBOXAMIDE'>0FK</scene><br>
			<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vbq\|3vbq]], [[3vbt\|3vbt]], [[3vbw\|3vbw]], [[3vbx\|3vbx]], [[3vby\|3vby]], [[3vc4\|3vc4]]</td></tr>
			<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
			<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
			<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vbv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vbv RCSB], [http://www.ebi.ac.uk/pdbsum/3vbv PDBsum]</span></td></tr>
			<table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			We have studied the subtleties of fragment docking and binding using data generated in a Pim-1 kinase inhibitor program. Crystallographic and docking data analyses have been undertaken using inhibitor complexes derived from an in-house surface plasmon resonance (SPR) fragment screen, a virtual needle screen, and a de novo designed fragment inhibitor hybrid. These investigations highlight that fragments that do not fill their binding pocket can exhibit promiscuous hydrophobic interactions due to the lack of steric constraints imposed on them by the boundaries of said pocket. As a result, docking modes that disagree with an observed crystal structure but maintain key crystallographically observed hydrogen bonds still have potential value in ligand design and optimization. This observation runs counter to the lore in fragment-based drug design that all fragment elaboration must be based on the parent crystal structure alone.

	<!--		Implications of Promiscuous Pim-1 Kinase Fragment Inhibitor Hydrophobic Interactions for Fragment-Based Drug Design.,Good AC, Liu J, Hirth B, Asmussen G, Xiang Y, Biemann HP, Bishop KA, Fremgen T, Fitzgerald M, Gladysheva T, Jain A, Jancsics K, Metz M, Papoulis A, Skerlj R, Stepp JD, Wei RR J Med Chem. 2012 Mar 5. PMID:22339127<ref>PMID:22339127</ref>
	~~The line below this paragraph~~, ~~containing "STRUCTURE_3vbv"~~, ~~creates the "Structure Box" on the page~~.
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display~~.
	-->
	~~{{STRUCTURE_3vbv\| PDB=3vbv \| SCENE= }}~~

	~~===Exploitation~~ of ~~hydrogen bonding constraints and flat hydrophobic energy landscapes in Pim-1 kinase needle screening and inhibitor design===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>

			==See Also==
	~~<!--~~		*[[Proto-oncogene serine/threonine-protein kinase\|Proto-oncogene serine/threonine-protein kinase]]
	~~The line below this paragraph, {{ABSTRACT_PUBMED_22339127}}, adds the Publication Abstract to the page~~		== References ==
	~~(as it appears on PubMed at http://www.pubmed.gov), where 22339127 is the PubMed ID number.~~		<references/>
	~~-->~~		__TOC__
	~~{{ABSTRACT_PUBMED_22339127}}~~		</StructureSection>

	==~~About this Structure~~==
	[[~~3vbv]] is a 1 chain structure with sequence from [http:~~//~~en.wikipedia.org/wiki/Homo_sapiens Homo sapiens~~]~~. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VBV OCA~~].

	==~~Reference~~==
	<~~ref group="xtra">PMID:022339127<~~/~~ref~~><~~references group="xtra"~~/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA at 08:26, 16 May 2012

2012-05-16T08:26:12Z

← Older revision		Revision as of 08:26, 16 May 2012
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	[[Image:3vbv.~~jpg~~\|left\|200px]]		[[Image:3vbv.png\|left\|200px]]

	<!--		<!--

OCA at 07:36, 21 March 2012

2012-03-21T07:36:50Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:3vbv.jpg|left|200px]]
-The entry 3vbv is ON HOLD  until Paper Publication
+<!--
-Authors: Liu, J.
+===Exploitation of hydrogen bonding constraints and flat hydrophobic energy landscapes in Pim-1 kinase needle screening and inhibitor design===
-Description: Exploitation of hydrogen bonding constraints and flat hydrophobic energy landscapes in Pim-1 kinase needle screening and inhibitor design

OCA at 06:52, 1 February 2012

2012-02-01T06:52:37Z

← Older revision		Revision as of 06:52, 1 February 2012
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 3vbv is ON HOLD		The entry 3vbv is ON HOLD until Paper Publication

	Authors: Liu, J.		Authors: Liu, J.

	Description: Exploitation of hydrogen bonding constraints and flat hydrophobic energy landscapes in Pim-1 kinase needle screening and inhibitor design		Description: Exploitation of hydrogen bonding constraints and flat hydrophobic energy landscapes in Pim-1 kinase needle screening and inhibitor design

OCA: Protected "3vbv" [edit=sysop:move=sysop]

2012-01-11T06:00:46Z

Protected "3vbv" [edit=sysop:move=sysop]

← Older revision	Revision as of 06:00, 11 January 2012
(No difference)

OCA: New page: '''Unreleased structure''' The entry 3vbv is ON HOLD Authors: Liu, J. Description: Exploitation of hydrogen bonding constraints and flat hydrophobic energy landscapes in Pim-1 kinase n...

2012-01-11T06:00:45Z

New page: '''Unreleased structure''' The entry 3vbv is ON HOLD Authors: Liu, J. Description: Exploitation of hydrogen bonding constraints and flat hydrophobic energy landscapes in Pim-1 kinase n...

New page

'''Unreleased structure'''

The entry 3vbv is ON HOLD

Authors: Liu, J.

Description: Exploitation of hydrogen bonding constraints and flat hydrophobic energy landscapes in Pim-1 kinase needle screening and inhibitor design