26:
428:
293:
342:
915:
Shapiro R, Ruiz-Gutierrez M, Chen CZ (Sep 2000). "Analysis of the interactions of human ribonuclease inhibitor with angiogenin and ribonuclease A by mutagenesis: importance of inhibitor residues inside versus outside the C-terminal "hot spot"".
328:
at the base of each turn, as it passes from α-helix to β-strand. The αβ repeats alternate between 28 and 29 residues in length, effectively forming a 57-residue unit that corresponds to its genetic structure (each
877:
Suzuki M, Saxena SK, Boix E, Prill RJ, Vasandani VM, Ladner JE, Sung C, Youle RJ (Mar 1999). "Engineering receptor-mediated cytotoxicity into human ribonucleases by steric blockade of inhibitor interaction".
805:
Kobe B, Deisenhofer J (Dec 1996). "Mechanism of ribonuclease inhibition by ribonuclease inhibitor protein based on the crystal structure of its complex with ribonuclease A".
158:
1031:
249:. It is a major cellular protein, comprising ~0.1% of all cellular protein by weight, and appears to play an important role in regulating the lifetime of
324:. The parallel β-strands and α-helices form the inner and outer wall of the horseshoe, respectively. The structure appears to be stabilized by buried
94:
369:(fM) range under physiological conditions. Despite this high affinity, RI is able to bind a wide variety of RNases A despite their relatively low
106:
566:
Lee FS, Shapiro R, Vallee BL (Jan 1989). "Tight-binding inhibition of angiogenin and ribonuclease A by placental ribonuclease inhibitor".
1365:
1209:
1168:
1317:
1134:
836:"Molecular recognition of human angiogenin by placental ribonuclease inhibitor--an X-ray crystallographic study at 2.0 A resolution"
603:"Molecular recognition of human angiogenin by placental ribonuclease inhibitor--an X-ray crystallographic study at 2.0 A resolution"
542:
1326:
1240:
1024:
1286:
1193:
760:
Kobe B, Deisenhofer J (Mar 1995). "A structural basis of the interactions between leucine-rich repeats and protein ligands".
178:
1459:
1380:
1214:
474:
Kobe B, Deisenhofer J (1993). "Crystal structure of porcine ribonuclease inhibitor, a protein with leucine-rich repeats".
25:
1413:
1405:
1309:
1299:
1281:
1222:
1126:
354:
1163:
1105:
1068:
1017:
396:
Mammalian RIs are unable to bind certain pancreatic ribonuclease family members from other species. In particular,
1429:
1252:
1118:
1454:
1385:
1247:
166:
1360:
1338:
1304:
1063:
441:
1321:
1257:
1230:
1142:
1058:
264:(21.5%, compared to 9% in typical proteins) and commensurately lower in other hydrophobic residues, esp.
30:
Top view of porcine ribonuclease inhibitor, showing its horseshoe shape. The outer layer is composed of
1464:
1370:
409:
358:
350:
99:
162:
769:
663:
483:
119:
1235:
1150:
317:
239:
1073:
997:
903:
793:
689:
507:
260:
content (~6.5%, cf. 1.7% in typical proteins) and is sensitive to oxidation. RI is also rich in
1343:
968:
933:
895:
865:
822:
785:
738:
681:
632:
583:
548:
538:
499:
464:
370:
185:
153:
1078:
1044:
989:
958:
925:
887:
855:
847:
814:
777:
728:
720:
671:
622:
614:
575:
530:
491:
145:
1348:
1155:
374:
773:
667:
487:
1201:
1188:
1095:
860:
835:
733:
708:
627:
602:
433:
377:
structures of RI-RNase A complexes suggest that the interaction is governed largely by
362:
676:
651:
534:
1448:
1331:
378:
281:
111:
1001:
907:
693:
511:
412:, escape mammalian RI and have been noted to have differential cytotoxicity against
62:
1040:
797:
382:
345:
Ribonuclease I (yellow) and inhibitor (pink helixes) complex heterotetramer, Human.
246:
141:
1009:
75:
87:
1178:
309:
31:
851:
724:
709:"Onconase and amphinase, the antitumor ribonucleases from Rana pipiens oocytes"
618:
427:
993:
423:
401:
390:
385:. RI's affinity for ribonucleases is important, since many ribonucleases have
366:
325:
313:
301:
297:
273:
269:
35:
38:. The inner and outer diameters are roughly 2.1 nm and 6.7 nm, respectively.
1271:
963:
947:"A ribonuclease A variant with low catalytic activity but high cytotoxicity"
946:
405:
397:
386:
321:
972:
937:
929:
899:
818:
742:
685:
552:
292:
869:
826:
789:
636:
587:
503:
296:
Side view of porcine ribonuclease inhibitor; ribbon is colored from blue (
115:
980:
Yakovlev GI, Mitkevich VA, Makarov AA (2006). "Ribonuclease inhibitors".
320:
elements wrap around in a curved, right-handed solenoid that resembles a
308:
RI is the classic leucine-rich repeat protein, consisting of alternating
277:
257:
82:
579:
261:
242:
468:
221:
215:
209:
203:
197:
191:
1110:
781:
495:
413:
265:
173:
1395:
291:
891:
330:
135:
69:
57:
1013:
341:
652:"Cytotoxic ribonucleases: molecular weapons and their targets"
250:
529:. Methods in Enzymology. Vol. 341. pp. 611–28.
525:
Shapiro R (2001). "Cytoplasmic ribonuclease inhibitor".
238:
is a large (~450 residues, ~49 kDa), acidic (pI ~4.7),
393:
effects that correlate well with ability to bind RI.
353:
of RI for ribonucleases is among the highest for any
1422:
1394:
1270:
1177:
1094:
1087:
1051:
834:Papageorgiou AC, Shapiro R, Acharya KR (Sep 1997).
601:Papageorgiou AC, Shapiro R, Acharya KR (Sep 1997).
381:interactions, but also involves substantial buried
184:
172:
152:
134:
129:
105:
93:
81:
68:
56:
48:
43:
18:
245:that forms extremely tight complexes with certain
707:Ardelt W, Shogen K, Darzynkiewicz Z (Jun 2008).
1025:
945:Bretscher LE, Abel RL, Raines RT (Apr 2000).
459:
457:
8:
1091:
1032:
1018:
1010:
126:
24:
962:
859:
732:
675:
626:
340:
650:Makarov AA, Ilinskaya ON (April 2003).
453:
15:
7:
713:Current Pharmaceutical Biotechnology
951:The Journal of Biological Chemistry
14:
426:
373:. Both biochemical studies and
333:codes for a 57-residue unit).
1:
677:10.1016/s0014-5793(03)00225-4
535:10.1016/S0076-6879(01)41180-3
444:- a chemical RNase inhibitor.
130:Available protein structures:
918:Journal of Molecular Biology
807:Journal of Molecular Biology
355:protein-protein interaction
316:along its backbone. These
256:RI has a surprisingly high
236:Ribonuclease inhibitor (RI)
1481:
1210:Dihydropteroate synthetase
1069:Non-competitive inhibition
725:10.2174/138920108784567245
1430:Steroidogenesis inhibitor
994:10.1134/S0026893306060045
125:
23:
1366:Matrix metalloproteinase
1169:Ribonucleotide reductase
1064:Uncompetitive inhibition
852:10.1093/emboj/16.17.5162
619:10.1093/emboj/16.17.5162
337:Binding to ribonucleases
1135:Dihydrofolate reductase
964:10.1074/jbc.275.14.9893
442:Guanidinium thiocyanate
34:and the inner layer of
1231:Nucleotidyltransferase
1059:Competitive inhibition
930:10.1006/jmbi.2000.4075
819:10.1006/jmbi.1996.0694
527:Ribonucleases - Part A
346:
305:
1241:Reverse transcriptase
410:Northern leopard frog
359:dissociation constant
344:
295:
1460:Hydrolase inhibitors
1287:Acetylcholinesterase
1194:Thymidylate synthase
880:Nature Biotechnology
1381:Histone deacetylase
1215:Farnesyltransferase
774:1995Natur.374..183K
668:2003FEBSL.540...15M
580:10.1021/bi00427a031
488:1993Natur.366..751K
318:secondary structure
240:leucine-rich repeat
19:Leucine Rich Repeat
1414:Carbonic anhydrase
1406:Dopa decarboxylase
1074:Suicide inhibition
365:complex is in the
347:
306:
36:parallel β-strands
1442:
1441:
1438:
1437:
1310:Alpha-glucosidase
1300:Polygalacturonase
1282:Phosphodiesterase
1223:GABA transaminase
1127:Monoamine oxidase
1111:HMG-CoA reductase
1045:enzyme inhibition
982:Molecular Biology
371:sequence identity
233:
232:
229:
228:
179:structure summary
1472:
1164:Xanthine oxidase
1106:Aldose reductase
1092:
1079:Mixed inhibition
1034:
1027:
1020:
1011:
1005:
976:
966:
941:
911:
873:
863:
840:The EMBO Journal
830:
801:
782:10.1038/374183a0
747:
746:
736:
704:
698:
697:
679:
647:
641:
640:
630:
607:The EMBO Journal
598:
592:
591:
563:
557:
556:
522:
516:
515:
496:10.1038/366751a0
471:
461:
436:
431:
430:
375:crystallographic
224:
218:
212:
206:
200:
194:
127:
28:
16:
1480:
1479:
1475:
1474:
1473:
1471:
1470:
1469:
1455:Protein domains
1445:
1444:
1443:
1434:
1418:
1390:
1266:
1253:Tyrosine kinase
1173:
1083:
1047:
1038:
1008:
979:
944:
914:
876:
846:(17): 5162–77.
833:
804:
768:(6518): 183–6.
759:
755:
753:Further reading
750:
706:
705:
701:
649:
648:
644:
613:(17): 5162–77.
600:
599:
595:
565:
564:
560:
545:
524:
523:
519:
482:(6457): 751–6.
473:
463:
462:
455:
451:
432:
425:
422:
339:
290:
220:
214:
208:
202:
196:
190:
39:
12:
11:
5:
1478:
1476:
1468:
1467:
1462:
1457:
1447:
1446:
1440:
1439:
1436:
1435:
1433:
1432:
1426:
1424:
1420:
1419:
1417:
1416:
1409:
1408:
1401:
1399:
1392:
1391:
1389:
1388:
1386:Beta-lactamase
1383:
1376:
1375:
1374:
1373:
1368:
1363:
1353:
1352:
1351:
1346:
1336:
1335:
1334:
1329:
1313:
1312:
1307:
1302:
1295:
1294:
1289:
1284:
1277:
1275:
1268:
1267:
1265:
1264:
1263:
1262:
1261:
1260:
1248:Protein kinase
1245:
1244:
1243:
1238:
1226:
1225:
1218:
1217:
1212:
1205:
1204:
1197:
1196:
1191:
1184:
1182:
1175:
1174:
1172:
1171:
1166:
1159:
1158:
1153:
1146:
1145:
1138:
1137:
1130:
1129:
1122:
1121:
1114:
1113:
1108:
1101:
1099:
1096:Oxidoreductase
1089:
1085:
1084:
1082:
1081:
1076:
1071:
1066:
1061:
1055:
1053:
1049:
1048:
1039:
1037:
1036:
1029:
1022:
1014:
1007:
1006:
988:(6): 867–874.
977:
957:(14): 9893–6.
942:
924:(2): 497–519.
912:
874:
831:
813:(5): 1028–43.
802:
756:
754:
751:
749:
748:
699:
662:(1–3): 15–20.
642:
593:
558:
543:
517:
452:
450:
447:
446:
445:
438:
437:
434:Biology portal
421:
418:
338:
335:
289:
286:
231:
230:
227:
226:
188:
182:
181:
176:
170:
169:
156:
150:
149:
139:
132:
131:
123:
122:
109:
103:
102:
97:
91:
90:
85:
79:
78:
73:
66:
65:
60:
54:
53:
50:
46:
45:
41:
40:
29:
21:
20:
13:
10:
9:
6:
4:
3:
2:
1477:
1466:
1463:
1461:
1458:
1456:
1453:
1452:
1450:
1431:
1428:
1427:
1425:
1423:Miscellaneous
1421:
1415:
1411:
1410:
1407:
1403:
1402:
1400:
1397:
1393:
1387:
1384:
1382:
1378:
1377:
1372:
1369:
1367:
1364:
1362:
1361:Enkephalinase
1359:
1358:
1357:
1354:
1350:
1347:
1345:
1342:
1341:
1340:
1339:Endopeptidase
1337:
1333:
1330:
1328:
1325:
1324:
1323:
1319:
1315:
1314:
1311:
1308:
1306:
1305:Neuraminidase
1303:
1301:
1297:
1296:
1293:
1290:
1288:
1285:
1283:
1279:
1278:
1276:
1273:
1269:
1259:
1256:
1255:
1254:
1251:
1250:
1249:
1246:
1242:
1239:
1237:
1234:
1233:
1232:
1228:
1227:
1224:
1220:
1219:
1216:
1213:
1211:
1207:
1206:
1203:
1199:
1198:
1195:
1192:
1190:
1186:
1185:
1183:
1180:
1176:
1170:
1167:
1165:
1161:
1160:
1157:
1154:
1152:
1148:
1147:
1144:
1140:
1139:
1136:
1132:
1131:
1128:
1124:
1123:
1120:
1116:
1115:
1112:
1109:
1107:
1103:
1102:
1100:
1097:
1093:
1090:
1086:
1080:
1077:
1075:
1072:
1070:
1067:
1065:
1062:
1060:
1057:
1056:
1054:
1050:
1046:
1042:
1035:
1030:
1028:
1023:
1021:
1016:
1015:
1012:
1003:
999:
995:
991:
987:
983:
978:
974:
970:
965:
960:
956:
952:
948:
943:
939:
935:
931:
927:
923:
919:
913:
909:
905:
901:
897:
893:
889:
886:(3): 265–70.
885:
881:
875:
871:
867:
862:
857:
853:
849:
845:
841:
837:
832:
828:
824:
820:
816:
812:
808:
803:
799:
795:
791:
787:
783:
779:
775:
771:
767:
763:
758:
757:
752:
744:
740:
735:
730:
726:
722:
719:(3): 215–25.
718:
714:
710:
703:
700:
695:
691:
687:
683:
678:
673:
669:
665:
661:
657:
653:
646:
643:
638:
634:
629:
624:
620:
616:
612:
608:
604:
597:
594:
589:
585:
581:
577:
574:(1): 225–30.
573:
569:
562:
559:
554:
550:
546:
544:9780121822422
540:
536:
532:
528:
521:
518:
513:
509:
505:
501:
497:
493:
489:
485:
481:
477:
470:
466:
460:
458:
454:
448:
443:
440:
439:
435:
429:
424:
419:
417:
415:
411:
407:
403:
400:RNases, such
399:
394:
392:
388:
384:
380:
379:electrostatic
376:
372:
368:
364:
360:
356:
352:
343:
336:
334:
332:
327:
323:
319:
315:
311:
303:
299:
294:
287:
285:
283:
282:phenylalanine
279:
275:
271:
267:
263:
259:
254:
252:
248:
247:ribonucleases
244:
241:
237:
223:
217:
211:
205:
199:
193:
189:
187:
183:
180:
177:
175:
171:
168:
164:
160:
157:
155:
151:
147:
143:
140:
137:
133:
128:
124:
121:
117:
113:
110:
108:
104:
101:
98:
96:
92:
89:
86:
84:
80:
77:
74:
71:
67:
64:
61:
59:
55:
51:
47:
42:
37:
33:
27:
22:
17:
1465:LRR proteins
1355:
1322:Exopeptidase
1292:Ribonuclease
1291:
1258:Janus kinase
1143:Lipoxygenase
1119:5α-Reductase
1041:Pharmacology
985:
981:
954:
950:
921:
917:
892:10.1038/7010
883:
879:
843:
839:
810:
806:
765:
761:
716:
712:
702:
659:
656:FEBS Letters
655:
645:
610:
606:
596:
571:
568:Biochemistry
567:
561:
526:
520:
479:
475:
395:
383:surface area
348:
307:
255:
235:
234:
1371:Oxytocinase
1179:Transferase
326:asparagines
44:Identifiers
1449:Categories
449:References
402:ranpirnase
391:cytostatic
367:femtomolar
361:of the RI-
302:C-terminus
300:) to red (
298:N-terminus
274:methionine
270:isoleucine
142:structures
1272:Hydrolase
1236:Integrase
1151:Aromatase
1088:Substrate
472:;
408:from the
406:amphinase
398:amphibian
387:cytotoxic
322:horseshoe
314:β-strands
310:α-helices
288:Structure
219:,
213:,
207:,
201:,
195:,
88:IPR003590
32:α-helices
1318:Protease
1002:31887913
973:10744660
938:10970748
908:23140257
900:10096294
743:18673287
694:30324366
686:12681476
553:11582809
512:34579479
420:See also
351:affinity
278:tyrosine
258:cysteine
159:RCSB PDB
83:InterPro
1344:Trypsin
870:9311977
861:1170149
827:9000628
798:4364436
790:7877692
770:Bibcode
734:2586917
664:Bibcode
637:9311977
628:1170149
588:2706246
504:8264799
484:Bibcode
416:cells.
363:RNase A
262:leucine
243:protein
225:
100:SM00368
63:PF00560
1398:(EC 4)
1274:(EC 3)
1181:(EC 2)
1141:1.13
1098:(EC 1)
1000:
971:
936:
906:
898:
868:
858:
825:
796:
788:
762:Nature
741:
731:
692:
684:
635:
625:
586:
551:
541:
510:
502:
476:Nature
414:cancer
357:; the
280:, and
266:valine
174:PDBsum
148:
138:
120:SUPFAM
76:CL0022
49:Symbol
1396:Lyase
1356:Mixed
1349:Renin
1327:DPP-4
1162:1.17
1156:COX-2
1149:1.14
1052:Class
998:S2CID
904:S2CID
794:S2CID
690:S2CID
508:S2CID
116:SCOPe
107:SCOP2
95:SMART
52:LRR_1
1412:4.2
1404:4.1
1379:3.5
1316:3.4
1298:3.2
1280:3.1
1229:2.7
1221:2.6
1208:2.5
1202:PARP
1200:2.4
1189:COMT
1187:2.1
1133:1.5
1125:1.4
1117:1.3
1104:1.1
969:PMID
934:PMID
896:PMID
866:PMID
823:PMID
786:PMID
739:PMID
682:PMID
633:PMID
584:PMID
549:PMID
539:ISBN
500:PMID
469:2BNH
404:and
389:and
349:The
331:exon
312:and
222:2q4g
216:2bnh
210:2bex
204:1z7x
198:1dfj
192:1a4y
167:PDBj
163:PDBe
146:ECOD
136:Pfam
112:1bnh
72:clan
70:Pfam
58:Pfam
1332:ACE
990:doi
959:doi
955:275
926:doi
922:302
888:doi
856:PMC
848:doi
815:doi
811:264
778:doi
766:374
729:PMC
721:doi
672:doi
660:540
623:PMC
615:doi
576:doi
531:doi
492:doi
480:366
465:PDB
251:RNA
186:PDB
154:PDB
1451::
1320::
1043::
996:.
986:40
984:.
967:.
953:.
949:.
932:.
920:.
902:.
894:.
884:17
882:.
864:.
854:.
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